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Evaluation of the cytotoxicity, antioxidant activity, and molecular docking of biogenic zinc oxide nanoparticles derived from pumpkin seeds

Kadir NHA, Murugan N, Khan AA, Sandrasegaran A, Khan AU, Alam M

Microsc Res Tech, 2024 Mar;87(3):602-615.
PMID: 38018343 DOI: 10.1002/jemt.24437

This study aimed to investigate the characterization of zinc oxide nanoparticles (ZnONPs) produced from Cucurbita pepo L. (pumpkin seeds) and their selective cytotoxic effectiveness on human colon cancer cells (HCT 116) and African Green Monkey Kidney, Vero cells. The study also investigated the antioxidant activity of ZnONPs. The study also examined ZnONPs' antioxidant properties. This was motivated by the limited research on the comparative cytotoxic effects of ZnO NPs on normal and HCT116 cells. The ZnO NPs were characterized using Fourier-transform infrared spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Transmission Electron Microscope/Selected Area Electron Diffraction (TEM/SAED), and Scanning Electron Microscope-Energy Dispersive X-ray (SEM-EDX) for determination of chemical fingerprinting, heat stability, size, and morphology of the elements, respectively. Based on the results, ZnO NPs from pumpkins were found to be less than 5 μm and agglomerates in nature. Furthermore, the ZnO NPs fingerprinting and SEM-EDX element analysis were similar to previous literature, suggesting the sample was proven as ZnO NPs. The ZnO NPs also stable at a temperature of 380°C indicating that the green material is quite robust at 60-400°C. The cell viability of Vero cells and HCT 116 cell line were measured at two different time points (24 and 48 h) to assess the cytotoxicity effects of ZnO NP on these cells using AlamarBlue assay. Cytotoxic results have shown that ZnO NPs did not inhibit Vero cells but were slightly toxic to cancer cells, with a dose-response curve IC50 = ~409.7 μg/mL. This green synthesis of ZnO NPs was found to be non-toxic to normal cells but has a slight cytotoxicity effect on HCT 116 cells. A theoretical study used molecular docking to investigate nanoparticle interaction with cyclin-dependent kinase 2 (CDK2), exploring its mechanism in inhibiting CDK2's role in cancer. Further study should be carried out to determine suitable concentrations for cytotoxicity studies. Additionally, DPPH has a significant antioxidant capacity, with an IC50 of 142.857 μg/mL. RESEARCH HIGHLIGHTS: Pumpkin seed extracts facilitated a rapid, high-yielding, and environmentally friendly synthesis of ZnO nanoparticles. Spectrophotometric analysis was used to investigate the optical properties, scalability, size, shape, dispersity, and stability of ZnO NPs. The cytotoxicity of ZnO NPs on Vero and HCT 116 cells was assessed, showing no inhibition of Vero cells and cytotoxicity of cancer cells. The DPPH assay was also used to investigate the antioxidant potential of biogenic nanoparticles. A molecular docking study was performed to investigate the interaction of ZnO NPs with CDK2 and to explore the mechanism by which they inhibit CDK2's role in cancer.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Antioxidants/pharmacology; Plant Extracts/pharmacology
Synergistic effects of CuO/TiO2 -chitosan-farnesol nanocomposites: Synthesis, characterization, antimicrobial, and anticancer activities on melanoma cells SK-MEL-3

Indumathi T, Suriyaprakash J, Alarfaj AA, Hirad AH, Jaganathan R, Mathanmohun M

J Basic Microbiol, 2024 Feb;64(2):e2300505.
PMID: 37988658 DOI: 10.1002/jobm.202300505

The current investigation focuses on synthesizing copper oxide (CuO)-titanium oxide (TiO2 )-chitosan-farnesol nanocomposites with potential antibacterial, antifungal, and anticancer properties against Melanoma cells (melanoma cells [SK-MEL-3]). The nanocomposites were synthesized using the standard acetic acid method and subsequently characterized using an X-ray diffractometer, scanning electron microscope, transmission electron microscopy, and Fourier transform infrared spectroscopy. The results from the antibacterial tests against Streptococcus pneumoniae and Stapylococcus aureus demonstrated significant antibacterial efficacy. Additionally, the antifungal studies using Candida albicans through the agar diffusion method displayed a considerable antifungal effect. For evaluating the anticancer activity, various assays such as MTT assay, acridine orange/ethidium bromide dual staining assay, reactive oxygen species (ROS) generation assay, and mitochondrial membrane potential (MMP) analysis were conducted on SK-MEL-3 cells. The nanocomposites exhibited the ability to induce ROS generation, decrease MMP levels, and trigger apoptosis in SK-MEL-3 cells. Collectively, the findings demonstrated a distinct pattern for the synthesized bimetallic nanocomposites. Furthermore, these nanocomposites also displayed significant (p

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Antifungal Agents/pharmacology; Copper/pharmacology
Fulltext Herbicidal properties of antihypertensive drugs: calcium channel blockers

Abdullah HSTSH, Chia PW, Omar D, Chuah TS

Sci Rep, 2021 07 09;11(1):14227.
PMID: 34244589 DOI: 10.1038/s41598-021-93662-2

Herbicide resistance is a worldwide problem in weed control. This prompts researchers to look for new modes of action to slow down the evolution of herbicide-resistant weeds. This research aims to determine the herbicidal action of thiazolo[3,2-a]pyrimidines derivatives, which are well known as antihypertensive drugs. The phytotoxic effects of ten compounds were investigated using leaf disc discoloration test and seed germination bioassay. At concentrations of 125 to 250 mg/L, the 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (c) was highly active against Oldenlandia verticillata and Eleusine indica. At application rates of 1.25 to 2.5 kg ai/ha, formulated c demonstrated selective post-emergence and pre-emergence herbicidal activity against O. verticillata, E. indica and Cyperus iria. In the crop tolerance test, formulated c outperformed the commercial herbicide diuron, with aerobic Oryza sativa being the most tolerant, followed by Zea mays, and Brassica rapa. The addition of calcium chloride partially nullified compound c's inhibitory effects on weed shoot growth, indicating that it has potential as a calcium channel blocker. Compound c acted by triggering electrolyte leakage without affecting photosystem II. These findings imply that c could be explored further as a template for developing new herbicides with novel modes of action.

Matched MeSH terms: Antihypertensive Agents/pharmacology*; Calcium Channel Blockers/pharmacology*; Herbicides/pharmacology*
Fulltext New insights of phenolic compounds from optimized fruit extract of Ficus auriculata

Shahinuzzaman M, Akhtar P, Amin N, Ahmed Y, Anuar FH, Misran H, et al.

Sci Rep, 2021 Jun 14;11(1):12503.
PMID: 34127747 DOI: 10.1038/s41598-021-91913-w

In this study, the extraction conditions extracted maximize amounts of phenolic and bioactive compounds from the fruit extract of Ficus auriculata by using optimized response surface methodology. The antioxidant capacity was evaluated through the assay of radical scavenging ability on DPPH and ABTS as well as reducing power assays on total phenolic content (TPC). For the extraction purpose, the ultrasonic assisted extraction technique was employed. A second-order polynomial model satisfactorily fitted to the experimental findings concerning antioxidant activity (R2 = 0.968, P

Matched MeSH terms: Antioxidants/pharmacology; Phenols/pharmacology; Plant Extracts/pharmacology
Synthesis and characterization of marine seagrass (Cymodocea serrulata) mediated titanium dioxide nanoparticles for antibacterial, antibiofilm and antioxidant properties

Narayanan M, Srinivasan S, Gnanasekaran C, Ramachandran G, Chelliah CK, Rajivgandhi G, et al.

Microb Pathog, 2024 Apr;189:106595.
PMID: 38387848 DOI: 10.1016/j.micpath.2024.106595

Cymodocea serrulata mediated titanium dioxide nanoparticles (TiO2 NPs) were successfully synthesized. The XRD pattern and FTIR spectra demonstrated the crystalline structure of TiO2 NPs and the presence of phenols, flavonoids and alkaloids in the extract. Further SEM revealed that TiO2 NPs has uniform structure and spherical in shape with their size ranged from 58 to 117 nm. Antibacterial activity of TiO2 NPs against methicillin-resistant Staphylococcus aureus (MRSA) and Vibrio cholerae (V. cholerae), provided the zone of inhibition of 33.9 ± 1.7 and 36.3 ± 1.9 mm, respectively at 100 μg/mL concentration. MIC of TiO2 NPs against MRSA and V. cholerae showed 84% and 87% inhibition at 180 μg/mL and 160 μg/mL respectively. Subsequently, the sub-MIC of V. cholerae demonstrated minimal or no impact on bacterial growth at concentration of 42.5 μg/mL concentration. In addition, TiO2 NPs exhibited their ability to inhibit the biofilm forming V. cholerae which caused distinct morphological and intercellular damages analysed using CLSM and TEM. The antioxidant properties of TiO2 NPs were demonstrated through TAA and DPPH assays and exposed its scavenging activity with IC50 value of 36.42 and 68.85 μg/mL which denotes its valuable antioxidant properties with potential health benefits. Importantly, the brine shrimp based lethality experiment yielded a low cytotoxic effect with 13% mortality at 100 μg/mL. In conclusion, the multifaceted attributes of C. serrulata mediated TiO2 NPs encompassed the antibacterial, antioxidant and anti-biofilm inhibition effects with low cytotoxicity in nature were highlighted in this study and proved the bioderived TiO2 NPs could be used as a promising agent for biomedical applications.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Antioxidants/pharmacology; Plant Extracts/pharmacology
Fulltext Antioxidant and cytotoxic activities of three species of tropical seaweeds

Chia YY, Kanthimathi MS, Khoo KS, Rajarajeswaran J, Cheng HM, Yap WS

BMC Complement Altern Med, 2015;15:339.
PMID: 26415532 DOI: 10.1186/s12906-015-0867-1

Three species of seaweeds (Padina tetrastromatica, Caulerpa racemosa and Turbinaria ornata) are widely consumed by Asians as nutraceutical food due to their antioxidant properties. Studies have shown that these seaweeds exhibit bioactivities which include antimicrobial, antiviral, anti-hypertensive and anticoagulant activities. However, investigations into the mechanisms of action pertaining to the cytotoxic activity of the seaweeds are limited. The aim of this study was to determine the antioxidant and cytotoxic activities of whole extracts of P. tetrastromatica, C. racemosa and T. ornata, including the cellular events leading to the apoptotic cell death of the extract treated-MCF-7 cells. Bioassay guided fractionation was carried out and the compounds identified.

Matched MeSH terms: Antihypertensive Agents/pharmacology; Antioxidants/pharmacology*; Plant Extracts/pharmacology*
Fulltext Pharmacological screening of methanolic extract of Ixora species

Latha LY, Darah I, Jain K, Sasidharan S

Asian Pac J Trop Biomed, 2012 Feb;2(2):149-51.
PMID: 23569886 DOI: 10.1016/S2221-1691(11)60210-4

OBJECTIVE: To investigate the antimicrobial activity of methanolic extracts of different parts of Ixora species.
METHODS: Antimicrobial activity was carried out using disc diffusion assay against fungi, gram-positive and gram-negative bacteria.
RESULTS: All methanolic extracts of different parts of Ixora species showed a broad-spectrum of antibacterial and antiyeast activities, which inhibited the growth of at least one bacterium or yeast. There was no remarkable difference between different Ixora species observed in this study.
CONCLUSIONS: The significant antimicrobial activity shown by this Ixora species suggests its potential against infections caused by pathogens. The extract may be developed as an antimicrobial agent.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Antifungal Agents/pharmacology; Plant Extracts/pharmacology*
Fulltext Carbon nanodots as molecular scaffolds for development of antimicrobial agents

Ngu-Schwemlein M, Chin SF, Hileman R, Drozdowski C, Upchurch C, Hargrove A

Bioorg Med Chem Lett, 2016 Apr 01;26(7):1745-9.
PMID: 26923697 DOI: 10.1016/j.bmcl.2016.02.047

We report the potential of carbon nanodots (CNDs) as a molecular scaffold for enhancing the antimicrobial activities of small dendritic poly(amidoamines) (PAMAM). Carbon nanodots prepared from sago starch are readily functionalized with PAMAM by using N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Electron microscopy images of these polyaminated CNDs show that they are approximately 30-60nm in diameter. Infrared and fluorescence spectroscopy analyses of the water-soluble material established the presence of the polyamidoaminated moiety and the intrinsic fluorescence of the nanodots. The polyaminated nanodots (CND-PAM1 and CND-PAM2) exhibit in vitro antimicrobial properties, not only to non-multidrug resistant bacteria but also to the corresponding Gram-negative multidrug bacteria. Their minimum inhibitory concentration (MIC) ranges from 8 to 64μg/mL, which is much lower than that of PAMAM G1 or the non-active PAMAM G0 and CNDs. Additionally, they show synergistic effect in combination with tetracycline or colistin. These preliminary results imply that CNDs can serve as a promising scaffold for facilitating the rational design of antimicrobial materials for combating the ever-increasing threat of antibiotic resistance. Moreover, their fluorescence could be pertinent to unraveling their mode of action for imaging or diagnostic applications.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Carbon/pharmacology*; Dendrimers/pharmacology*
Salvia officinalis L. Methanolic Extract Reduces Lead and Nicotine-Induced Sperm Quality Degeneration in Male Rats

Ammar Aldaddou W, Aljohani ASM, Adewale Ahmed I, Al-Wabel NA, El-Ashmawy IM

Chem Biodivers, 2023 Jul;20(7):e202300115.
PMID: 37236909 DOI: 10.1002/cbdv.202300115

Most heavy metals and industrial chemicals such as nicotine and lead cause harm to the reproduction process through a decrease in sperm motility, fertilization process, and sperm binding to the oocyte. Salvia officinalis L. (sage) has been reported to enhance serum testosterone levels and other certain biochemical enzymes. Thus, the current study is aimed at evaluating the potential health benefits of S. officinalis L. methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC/MS). In the study, fifty-four mature male albino rats of about 220-250 g [were divided randomly and equally into 9 groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5 g/L of lead acetate in drinking water or peritoneal injection of 0.50 mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400 mg/kg b.w.) of S. officinalis L. were used. The rats were anesthetized after the experimental period and then sacrificed. Blood samples were collected while the epididymis, testicle, and accessory sex organs (prostates and seminal vesical) were taken for histopathological studies. Twelve major compounds were identified through the GC/MS analysis of S. officinalis L. methanol extract. Lead and nicotine toxicity had a great effect on the rats' sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs (accessory sex glands, epididymis, and testis). The administration of S. officinalis L. methanol extract, however, had a positive impact on the sexual organ weights, semen quality & quantity, and rats' fertility, thus, ameliorating the adversative effects of both lead and nicotine. Further evaluation and isolation of the bioactive components are recommended as potential drug leads.

Matched MeSH terms: Nicotine/pharmacology; Plant Extracts/pharmacology; Tartrates/pharmacology
Fulltext Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy

Yusoh NA, Tiley PR, James SD, Harun SN, Thomas JA, Saad N, et al.

J Med Chem, 2023 May 25;66(10):6922-6937.
PMID: 37185020 DOI: 10.1021/acs.jmedchem.3c00322

Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens.

Matched MeSH terms: Poly(ADP-ribose) Polymerase Inhibitors/pharmacology; Antineoplastic Combined Chemotherapy Protocols/pharmacology; Phthalazines/pharmacology
Fulltext Sargassum Seaweed as a Source of Anti-Inflammatory Substances and the Potential Insight of the Tropical Species: A Review

Saraswati, Giriwono PE, Iskandriati D, Tan CP, Andarwulan N

Mar Drugs, 2019 Oct 17;17(10).
PMID: 31627414 DOI: 10.3390/md17100590

Sargassum is recognized both empirically and scientifically as a potential anti-inflammatory agent. Inflammation is an important response in the body that helps to overcome various challenges to body homeostasis such as microbial infections, tissue stress, and certain injuries. Excessive and uncontrolled inflammatory conditions can affect the pathogenesis of various diseases. This review aims to explore the potential of Sargassum's anti-inflammatory activity, not only in crude extracts but also in sulfated polysaccharides and purified compounds. The tropical region has a promising availability of Sargassum biomass because its climate allows for the optimal growth of seaweed throughout the year. This is important for its commercial utilization as functional ingredients for both food and non-food applications. To the best of our knowledge, studies related to Sargassum's anti-inflammatory activity are still dominated by subtropical species. Studies on tropical Sargassum are mainly focused on the polysaccharides group, though there are some other potentially bioactive compounds such as polyphenols, terpenoids, fucoxanthin, fatty acids and their derivatives, typical polar lipids, and other groups. Information on the modulation mechanism of Sargassum's bioactive compounds on the inflammatory response is also discussed here, but specific mechanisms related to the interaction between bioactive compounds and targets in cells still need to be further studied.

Matched MeSH terms: Anti-Inflammatory Agents/pharmacology*; Polysaccharides/pharmacology; Polyphenols/pharmacology
Nutritional Value, Therapeutic Effects, Phytochemistry, and Toxicology of Lepisanthes fruticosa: A Review

Siang LJ, Rajak H, Ravichandran V

Curr Top Med Chem, 2024;24(15):1279-1290.
PMID: 38639276 DOI: 10.2174/0115680266300963240408051156

The multifaceted benefits of Lepisanthes fruticosa position it is not only as a promising agricultural commodity but also as a versatile resource with implications for health, biodiversity, and economic growth. Lepisanthes fruticosa has a rich history of traditional use for treating various ailments such as fever and diarrhea. Beyond its traditional uses, the plant's antioxidant properties suggest potential applications in combating oxidative stress-related conditions. Its antihyperglycemic properties indicate promise in managing elevated blood sugar levels, while its antibacterial and antiviral attributes hint at potential applications in infectious disease control. Furthermore, the plant's anticancer properties add to its appeal as a valuable resource in the realm of medical research. The plant also exhibits considerable potential in addressing a range of health concerns, including non-communicable diseases and infections, antidiarrheal, and antiviral properties. In essence, Lepisanthes fruticose emerges as more than just an agricultural asset. Its unique combination of nutritional richness, health benefits, and economic viability underscores its potential to become a valuable asset both locally and on the global stage. In this current review, we are discussed about the ethnopharmacology, nutritional value, therapeutic effects, phytochemistry, and toxicology of Lepisanthes fruticose.

Matched MeSH terms: Antioxidants/pharmacology; Hypoglycemic Agents/pharmacology; Plant Extracts/pharmacology
Fulltext Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

Boudriga S, Haddad S, Murugaiyah V, Askri M, Knorr M, Strohmann C, et al.

Molecules, 2020 Apr 23;25(8).
PMID: 32340203 DOI: 10.3390/molecules25081963

A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*; Pyrrolidines/pharmacology*; Spiro Compounds/pharmacology*
Efficacy of agnique (mmf) monomolecular surface film against immature stages of Anopheles arabiensis patton and Culex spp (diptera: culicidae) in Khartoum, Sudan

Bashir A, Hassan AA, Salmah MR, Rahman WA

Southeast Asian J Trop Med Public Health, 2008 Mar;39(2):222-8.
PMID: 18564706

The efficacy of the larvicidal and pupicidal agent (Agnique) MMF was evaluated against larvae of An. arabiensis and Culex (Diptera: Culicidae) under field conditions in Bahary Locality, Khartoum, Sudan. At an applied dosage of 0.25 ml/m2, MMF resulted in 89.4, 79.8 and 88.2% reductions in L3-L4 instars An. arabiensis and 63.5% in Culex larvae (all stages) 24 to 72 hours post-treatment. Pupae were completely eliminated (100%) within 24 hours posttreatment. The earlier instars (L1-L2) of An. arabiensis were more tolerant with a 62.5% reduction at 72 hours post-treatment compared to (L3-L4) instars and pupae. At 7-days post-treatment Agnique gave a 57.5% reduction in L1-L2 and 92.6% in L3-L4 instar larvae of An. arabiensis and 57.3% and 86.4% in Culex larvae and pupae, respectively. We conclude that Agnique can perform effectively against L3-L4 instars and pupae of An. arabiensis for only 1 week, and 3 to 4 days against L1-L2 instars of Culex spp.

Matched MeSH terms: Fatty Alcohols/pharmacology*; Polyethylene Glycols/pharmacology*; Surface-Active Agents/pharmacology*
Fulltext Rate of resistance development in wild Culex quinquefasciatus (Say) selected by malathion and permethrin

Nazni WA, Lee HL, Sa'diyah I

Southeast Asian J Trop Med Public Health, 1998 Dec;29(4):849-55.
PMID: 10772575

Wild caught female Culex quinquefasciatus (Say) from Kuala Lumpur were blood fed and reared in the insectarium. The late third stage of the F1 larvae which survived the high selection pressure of malathion and permethrin were reared and colonies were established from adults that emerged. Larvae from these colonies were then subjected in the subsequent 9 generations to higher selection pressure. The rate of resistance development were measured by LC50 value of larval bioassay, LT50 value of adult bioassay and the frequency of the elevated esterase levels. In another set of experiments using the same batch of Culex mosquitos, the larvae were not exposed to any insecticides and the decrease in resistance rate was monitored in each subsequent 9 generations by using similar methods. The heterozygous standard laboratory strain was selected for susceptibility using the single raft sib-selection method. The result showed that the field collected F1 generation was 96.0 and 6.3 fold more resistant to malathion and permethrin, respectively. After selection for about 9 generations the resistance ratio to malathion and permethrin was 6.2 and 767.3 fold more compared to the LC50 values of F1 generations, respectively. Esterase in F1 larvae was 6.0 fold more than the standard laboratory strain.

Matched MeSH terms: Insecticides/pharmacology*; Malathion/pharmacology*; Pyrethrins/pharmacology*
Toxicological studies of four insecticides against Musca domestica L

Yoke OP, Sudderuddin KI

Southeast Asian J Trop Med Public Health, 1975 Dec;6(4):525-31.
PMID: 818717

Toxicological studies of four insecticides (malathion, carbaryl, bioresmethrin, and GH 74) against Musca domestica vicinia (Ampang strain) were undertaken with particular reference to age, sex and posttreatment temperature. It was found that bioresmethrin and GH 74, both with a negative temperature coefficient, have great potential for use against houseflies. In vitro inhibitory studies of head and body esterases showed that unlike malathion and carbaryl, bioresmethrin had only negligible effect on these enzymes. The possibilities of using bioresmethrin and GH 74 for controlling the housefly problem in the Cameron Highlands, West Malaysia are discussed.

Matched MeSH terms: Malathion/pharmacology; Pyrethrins/pharmacology; Carbaryl/pharmacology
Designing potential lead compounds targeting aminoglycoside N (6')-acetyltransferase in Serratia marcescens: A drug discovery strategy

Prabhu D, Shankari G, Rajamanikandan S, Jeyakanthan J, Velusamy P, Gopinath SCB, et al.

Int J Biol Macromol, 2024 Nov;281(Pt 1):136976.
PMID: 39490491 DOI: 10.1016/j.ijbiomac.2024.136976

Serratia marcescens is an opportunistic human pathogen that causes urinary tract infections, ocular lens infections, and respiratory tract infections. S. marcescens employs various defense mechanisms to evade antibiotics, one of which is mediated by aminoglycoside N-acetyltransferase (AAC). In this mechanism, the enzyme AAC facilitates the transfer and linkage of the acetyl moiety from the donor substrate acetyl-coenzyme A to specific positions on antibiotics. This modification alters the antibiotic's structure, leading to the inactivation of aminoglycoside antibiotics. In the current scenario, antibiotic resistance has become a global threat, and targeting the enzymes that mediate resistance is considered crucial to combat this issue. The study aimed to address the increasing global threat of antibiotic resistance in Serratia marcescens by targeting the aminoglycoside N-acetyltransferase (AAC (6')) enzyme, which inactivates aminoglycoside antibiotics through acetylation. Due to the absence of experimental structure, we constructed a homology model of aminoglycoside N (6')-acetyltransferase (AAC (6')) of S. marcescens using the atomic structure of aminoglycoside N-acetyltransferase AAC (6')-Ib (PDB ID: 1V0C) as a template. The stable architecture and integrity of the modelled AAC (6') structure were analyzed through a 100 ns simulation. Structure-guided high-throughput screening of four small molecule databases (Binding, Life Chemicals, Zinc, and Toslab) resulted in the identification of potent inhibitors against AAC (6'). The hits obtained from screening were manually clustered, and the five hit molecules were shortlisted based on the docking score, which are observed in the range of -17.09 kcal/mol to -11.95 kcal/mol. These selected five molecules displayed acceptable pharmacological properties in ADME predictions. The binding free energy calculations, and molecular dynamics simulations of ligand bound AAC (6') complexes represented higher affinity and stable binding. The selected molecules demonstrated stable binding with AAC (6'), indicating their strong potential to hamper the binding of aminoglycoside in the respective site. and thereby inhibit. This process mitigates enzyme mediated AAC (6') activity on aminoglycosides and reverse the bactericidal function of aminoglycosides, and also this method could serve as a platform for the development of potential antimicrobials.

Matched MeSH terms: Aminoglycosides/pharmacology; Anti-Bacterial Agents/pharmacology; Enzyme Inhibitors/pharmacology
How Important is the Metal-free Catalytic Knoevenagel Reaction in Medicinal Chemistry? An Updated Review

Johari S, Johan MR, Khaligh NG

Curr Med Chem, 2024;31(27):4286-4311.
PMID: 38243980 DOI: 10.2174/0109298673260463231122074253

The Knoevenagel condensation is a powerful and primary step for the development of carbon-carbon bond transformations. These condensations offer versatile products/ intermediates for diverse uses in polymers, cosmetics, chemical industries, and medicinal chemistry. Various homogenous and heterogenous catalysts have been found to promote the Knoevenagel condensation reaction, both environmentally and economically. Due to their attractive use in the production of pharmaceutical drugs, they are proven to be the main force that drives the synthesis involving numerous multi-component and multistep reactions. The present study, therefore, aims to summarise reported Knoevenagel condensation reactions using metal-free catalysts resulting in pharmaceutically useful compounds with anti-cancer, anti-tumor, anti-oxidant, anti-malarial, anti-diabetic, and anti- bacterial activities. By considering factors like their structure-activity relationships (SARs), the reaction conditions, and the steps involved, as well as the advantages and limitations of the particular approach, we also provide a general framework and direction in order to achieve superior characteristics of the catalyst.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Antimalarials/pharmacology; Antineoplastic Agents/pharmacology
Fulltext Comparative efficacy of Knema retusa extract delivery via PEG-b-PCL, niosome, and their combination against Acanthamoeba triangularis genotype T4: characterization, inhibition, anti-adhesion, and cytotoxic activity

Chimplee S, Mitsuwan W, Zulkifli M, Eawsakul K, Ongtanasup T, Sangkanu S, et al.

PeerJ, 2024;12:e18452.
PMID: 39559326 DOI: 10.7717/peerj.18452

BACKGROUND: Acanthamoeba spp. is a waterborne, opportunistic protozoan that can cause amebic keratitis and granulomatous amebic encephalitis. Knema retusa is a native tree in Malaysia, and its extracts possess a broad range of biological activities. Niosomes are non-ionic surfactant-based vesicle formations and suggest a future targeted drug delivery system. Copolymer micelle (poly(ethylene glycol)-block-poly(ɛ-caprolactone); PEG-b-PCL) is also a key constituent of niosome and supports high stability and drug efficacy. To establish Knema retusa extract (KRe) loading in diverse nanocarriers via niosome, PEG-b-PCL micelle, and their combination and to study the effect of all types of nanoparticles (NPs) on Acanthamoeba viability, adherent ability, elimination of adherence, and cytotoxicity.
METHODS: In this study, we characterized niosomes, PEG-b-PCL, and their combination loaded with KRe and tested the effect of these NPs on Acanthamoeba triangularis stages. KRe-loaded PEG-b-PCL, KRe-loaded niosome, and KRe-loaded PEG-b-PCL plus niosome were synthesized and characterized regarding particle size and charge, yield, encapsulation efficiency (EE), and drug loading content (DLC). The effect of these KRe-loaded NPs on trophozoite and cystic forms of A. triangularis was assessed through assays of minimal inhibitory concentration (MIC), using trypan blue exclusion to determine the viability. The effect of KRe-loaded NPs was also determined on A. triangularis trophozoite for 24-72 h. Additionally, the anti-adhesion activity of the KRe-loaded niosome on trophozoites was also performed on a 96-well plate. Cytotoxicity activity of KRe-loaded NPs was assessed on VERO and HaCaT cells using MTT assay.
RESULTS: KRe-loaded niosome demonstrated a higher yielded (87.93 ± 6.03%) at 286 nm UV-Vis detection and exhibited a larger size (199.3 ± 29.98 nm) and DLC (19.63 ± 1.84%) compared to KRe-loaded PEG-b-PCL (45.2 ± 10.07 nm and 2.15 ± 0.25%). The EE (%) of KRe-loaded niosome was 63.67 ± 4.04, which was significantly lower than that of the combination of PEG-b-PCL and niosome (79.67 ± 2.08). However, the particle charge of these NPs was similar (-28.2 ± 3.68 mV and -28.5 ± 4.88, respectively). Additionally, KRe-loaded niosome and KRe-loaded PEG-b-PCL plus niosome exhibited a lower MIC at 24 h (0.25 mg/mL), inhibiting 90-100% of Acanthamoeba trophozoites which lasted 72 h. KRe-loaded niosome affected adherence by around 40-60% at 0.125-0.25 mg/mL and removed Acanthamoeba adhesion on the surface by about 90% at 0.5 mg/mL. Cell viability of VERO and HaCaT cells treated with 0.125 mg/mL of KRe-loaded niosome and KRe-loaded PEG-b-PCL plus niosome exceeded 80%.
CONCLUSION: Indeed, niosome and niosome plus PEG-b-PCL were suitable nanocarrier-loaded KRe, and they had a greater nanoparticle property to test with high activities against A. triangularis on the reduction of adherence ability and demonstration of its low toxicity to VERO and HaCaT cells.

Matched MeSH terms: Antiprotozoal Agents/pharmacology; Plant Extracts/pharmacology; Polyesters/pharmacology
Geographical patterns of in vitro susceptibilities to tigecycline and colistin among worldwide isolates of Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae: Data from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme, 2016-2021

Wang JL, Lai CC, Ko WC, Hsueh PR

Int J Antimicrob Agents, 2023 Sep;62(3):106930.
PMID: 37490959 DOI: 10.1016/j.ijantimicag.2023.106930

This study aimed to investigate the geographical trends of minimum inhibitory concentrations (MICs) for tigecycline and colistin in Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae isolates which were collected for the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme from 2016-2021. MICs of the isolates were determined using the broth microdilution method. In the study period, there was an increase in MIC50 and MIC90 values in Asia for tigecycline MICs in A. baumannii isolates, and the geometric mean of MICs increased significantly from 0.51-0.96 (R2 value of 0.912). The isolates in Europe and Latin America also showed an increase in the geometric mean, but the percentage of MIC values ≤ 2 mg/L decreased from 99.7% to 86.7% in Asia. Among the Asian countries studied, China (90.9%), Thailand (94.3%), and Malaysia (95.5%) showed the lower percentages of tigecycline MIC values ≤0.5 mg/L for E. coli isolates. In terms of colistin susceptibility among A. baumannii isolates, there was no increase in MIC50/ MIC90 or the geometric mean from 2016-2021. Compared to other continents, A. baumannii isolates in Europe had the highest MIC50 (0.5 mg/L), MIC90 (2 mg/L), and geometric mean (0.55 mg/L). For E. coli, the percentage of colistin MIC values ≤2 mg/L was consistently >98% in the study areas from 2016-2021. Among K. pneumoniae isolates, Europe and Latin America had higher geometric means of MICs (0.41 and 0.4 mg/L, respectively) and lower percentages of colistin MICs ≤2 mg/L than those in the other continents.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Colistin/pharmacology; Minocycline/pharmacology

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