Displaying publications 21 - 40 of 88 in total

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  1. Molecular docking, synthesis, and biological evaluation of naphthoquinone as potential novel scaffold for H5N1 neuraminidase inhibition
    Sharma G, Vasanth Kumar S, Wahab HA
    J Biomol Struct Dyn, 2018 01;36(1):233-242.
    PMID: 28013578 DOI: 10.1080/07391102.2016.1274271
    A series of dimeric naphthoquinones containing natural 2-hydroxy-1-4-naphthoquinone moiety was designed, synthesized, and evaluated against neuraminidase of H5N1 virus. p-hydroxy derivatives showed higher inhibition when compared to p-halogenated compounds. Molecular docking studies conducted with H5N1 neuraminidase clearly demonstrated different binding modes of the most active compound onto the open and closed conformations of loop 150. The results thus provide not only evidences of a novel scaffold evaluated as inhibitor, but also a rational explanation involving molecular modeling and the role of loop 150 in the binding.
  2. Determination of CYP3A4 Inducing Properties of Compounds Using a Laboratory-Developed Cell-Based Assay
    Seah TC, Tay YL, Tan HK, Muhammad TS, Wahab HA, Tan ML
    Int J Toxicol, 2015 08 12;34(5):454-68.
    PMID: 26268769 DOI: 10.1177/1091581815599335
    A cell-based assay to measure cytochrome P450 3A4 (CYP3A4) induction was developed to screen for potential CYP3A4 inducers. This 96-well format assay utilizes HepG2 cells transfected with a gene construct of CYP3A4 proximal promoter linked to green fluorescence protein (GFP) gene, and the expression of the GFP is then measured quantitatively. Bergamottin at 5 to 25 µmol/L produced low induction relative to the positive control. Both curcumin and lycopene were not found to affect the expression of GFP, suggesting no induction properties toward CYP3A4. Interestingly, resveratrol produced significant induction from 25 µmol/L onward, which was similar to omeprazole and may warrant further studies. In conclusion, the present study demonstrated that this cell-based assay can be used as a tool to evaluate the potential CYP3A4 induction properties of compounds. However, molecular docking data have not provided satisfactory pointers to differentiate between CYP3A4 inducers from noninducers or from inhibitors, more comprehensive molecular screening may be indicated.
  3. Fulltext Identification of potential dual -targets anti- toxoplasma gondii compounds through structure-based virtual screening and in-vitro studies
    Salin NH, Noordin R, Al-Najjar BO, Kamarulzaman EE, Yunus MH, Karim IZA, et al.
    PLoS One, 2020;15(5):e0225232.
    PMID: 32442170 DOI: 10.1371/journal.pone.0225232
    Toxoplasma gondii is the etiologic agent of toxoplasmosis, a disease which can lead to morbidity and mortality of the fetus and immunocompromised individuals. Due to the limited effectiveness or side effects of existing drugs, the search for better drug candidates is still ongoing. In this study, we performed structure-based screening of potential dual-targets inhibitors of active sites of T. gondii drug targets such as uracil phosphoribosyltransferase (UPRTase) and adenosine kinase (AK). First screening of virtual compounds from the National Cancer Institute (NCI) was performed via molecular docking. Subsequently, the hit compounds were tested in-vitro for anti- T. gondii effect using cell viability assay with Vero cells as host to determine cytotoxicity effects and drug selectivities. Clindamycin, as positive control, showed a selectivity index (SI) of 10.9, thus compounds with SI > 10.9 specifically target T. gondii proliferation with no significant effect on the host cells. Good anti- T. gondii effects were observed with NSC77468 (7-ethoxy-4-methyl-6,7-dihydro-5H-thiopyrano[2,3-d]pyrimidin-2-amine) which showed SI values of 25. This study showed that in-silico selection can serve as an effective way to discover potentially potent and selective compounds against T. gondii.
  4. Fulltext Computational study of nitro-benzylidene phenazine as dengue virus-2 NS2B-NS3 protease inhibitor
    Salin NH, Hariono M, Khalili NSD, Zakaria II, Saqallah FG, Mohamad Taib MNA, et al.
    Front Mol Biosci, 2022;9:875424.
    PMID: 36465554 DOI: 10.3389/fmolb.2022.875424
    According to the World Health Organisation (WHO), as of week 23 of 2022, there were more than 1,311 cases of dengue in Malaysia, with 13 deaths reported. Furthermore, there was an increase of 65.7% during the same period in 2021. Despite the increase in cumulative dengue incidence, there is no effective antiviral drug available for dengue treatment. This work aimed to evaluate several nitro-benzylidene phenazine compounds, especially those that contain 4-hydroxy-3,5-bis((2-(4-nitrophenyl)hydrazinylidene)-methyl)benzoate through pharmacophore queries selection method as potential dengue virus 2 (DENV2) NS2B-NS3 protease inhibitors. Herein, molecular docking was employed to correlate the energies of selected hits' free binding and their binding affinities. Pan assay interference compounds (PAINS) filter was also adopted to identify and assess the drug-likeness, toxicity, mutagenicity potentials, and pharmacokinetic profiles to select hit compounds that can be considered as lead DENV2 NS2B-NS3 protease inhibitors. Molecular dynamics assessment of two nitro-benzylidene phenazine derivatives bearing dinitro and hydroxy groups at the benzylidene ring showed their stability at the main binding pocket of DENV2 protease, where their MM-PBSA binding energies were between -22.53 and -17.01 kcal/mol. This work reports those two nitro-benzylidene phenazine derivatives as hits with 52-55% efficiency as antiviral candidates. Therefore, further optimisation is required to minimise the lead compounds' toxicity and mutagenicity.
  5. Fulltext Multi-population Black Hole Algorithm for the problem of data clustering
    Salih SQ, Alsewari AA, Wahab HA, Mohammed MKA, Rashid TA, Das D, et al.
    PLoS One, 2023;18(7):e0288044.
    PMID: 37406006 DOI: 10.1371/journal.pone.0288044
    The retrieval of important information from a dataset requires applying a special data mining technique known as data clustering (DC). DC classifies similar objects into a groups of similar characteristics. Clustering involves grouping the data around k-cluster centres that typically are selected randomly. Recently, the issues behind DC have called for a search for an alternative solution. Recently, a nature-based optimization algorithm named Black Hole Algorithm (BHA) was developed to address the several well-known optimization problems. The BHA is a metaheuristic (population-based) that mimics the event around the natural phenomena of black holes, whereby an individual star represents the potential solutions revolving around the solution space. The original BHA algorithm showed better performance compared to other algorithms when applied to a benchmark dataset, despite its poor exploration capability. Hence, this paper presents a multi-population version of BHA as a generalization of the BHA called MBHA wherein the performance of the algorithm is not dependent on the best-found solution but a set of generated best solutions. The method formulated was subjected to testing using a set of nine widespread and popular benchmark test functions. The ensuing experimental outcomes indicated the highly precise results generated by the method compared to BHA and comparable algorithms in the study, as well as excellent robustness. Furthermore, the proposed MBHA achieved a high rate of convergence on six real datasets (collected from the UCL machine learning lab), making it suitable for DC problems. Lastly, the evaluations conclusively indicated the appropriateness of the proposed algorithm to resolve DC issues.
  6. The inhibitory effects of mitragynine on P-glycoprotein in vitro
    Rusli N, Amanah A, Kaur G, Adenan MI, Sulaiman SF, Wahab HA, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2019 04;392(4):481-496.
    PMID: 30604191 DOI: 10.1007/s00210-018-01605-y
    Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.
  7. Anti-Cholinesterase Activity of Chalcone Derivatives: Synthesis, In Vitro Assay and Molecular Docking Study
    Riswanto FDO, Rawa MSA, Murugaiyah V, Salin NH, Istyastono EP, Hariono M, et al.
    Med Chem, 2021;17(5):442-452.
    PMID: 31808389 DOI: 10.2174/1573406415666191206095032
    BACKGROUND: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase).

    OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

    METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method.

    RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 μM and 68.7 μM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288.

    CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.

  8. Fulltext The influence of leadership quality towards community cohesion in Iban community in Malaysia
    Rezaul Islam M, Wahab HA, Anggum LA
    Heliyon, 2020 Feb;6(2):e03370.
    PMID: 32072057 DOI: 10.1016/j.heliyon.2020.e03370
    This study aimed to examine the influence of the traditional leadership qualities towards to develop community cohesion in the Iban community in Malaysia. A quantitative approach was used to conduct this study, where data were collected through a self-administered survey questionnaire from 210 chiefs in the Iban longhouse at the Pakan District in Sarawak, Malaysia. A pre-tested questionaire was administrered to the respondents using a simple random sampling in the District of Pakan, Sarawak. The leadership quality was measured based on the leadership traits, leadership style, leadership behaviour, situational leadership, and trsnformational leadership; while the community cohesion was measured by a sense of belonging, social alienation, social support, rootedness, social solidarity, and social ties. The results of the correlation and regression analysis showed that the traditional leadership qualities had a significant correlation with the development of social cohesion. The findings proved that the traditional leadership is essential to increase community cohesion in the Iban community. The findings would be important guideline to the development thinkers, practitioners, community leaders, and development institutions.
  9. A new peptaibol, RK-026A, from the soil fungus Trichoderma sp. RK10-F026 by culture condition-dependent screening
    Rawa MSA, Nogawa T, Okano A, Futamura Y, Nakamura T, Wahab HA, et al.
    Biosci Biotechnol Biochem, 2021 Jan 07;85(1):69-76.
    PMID: 33577647 DOI: 10.1093/bbb/zbaa051
    A new peptaibol, RK-026A (1) was isolated from a fungus, Trichoderma sp. RK10-F026, along with atroviridin B (2), alamethicin II (3), and polysporin B (4) as a cytotoxic compound, which was selected by principal component analysis of the MS data from 5 different culture conditions. The structure of 1 was determined as a new atroviridin B derivative containing Glu at the 18th residue instead of Gln by NMR and HR-MS analyses including the investigation of detailed MS/MS fragmentations. 1 showed cytotoxicity toward K562 leukemia cells at an IC50 value of 4.1 µm.
  10. Zealpeptaibolin, an 11-mer cytotoxic peptaibol group with 3 Aib-Pro motifs isolated from Trichoderma sp. RK10-F026
    Rawa MSA, Nogawa T, Okano A, Futamura Y, Wahab HA, Osada H
    J Antibiot (Tokyo), 2021 08;74(8):485-495.
    PMID: 34163024 DOI: 10.1038/s41429-021-00429-y
    Six new 11-mer peptaibols designed as zealpeptaibolins, A - F were isolated from the soil fungus, Trichoderma sp. RK10-F026, based on the principal component analysis of the MS data from five different culture compositions. Previously, 20-mer peptaibols from the same fungal strain were identified; 11-mer peptaibols in contrast were discovered from a different culture condition, signifying peptaibol production was culture condition-dependent. These peptaibols contained three Aib-Pro motifs in the sequence. The structures were established by NMR and HR-MS experiments including detailed MS/MS fragmentations. The absolute configurations were determined by Marfey's analysis. Zealpeptaibolin F exhibited the strongest cytotoxicity toward K562 leukemia cells with an IC50 value of 0.91 µM.
  11. Analysis of secondary structure predictions of dengue virus type 2 NS2B/NS3 against crystal structure to evaluate the predictive power of the in silico methods
    Othman R, Wahab HA, Yusof R, Rahman NA
    In Silico Biol. (Gedrukt), 2007;7(2):215-24.
    PMID: 17688447
    Multiple sequence alignment was performed against eight proteases from the Flaviviridae family using ClustalW to illustrate conserved domains. Two sets of prediction approaches were applied and the results compared. Firstly, secondary structure prediction was performed using available structure prediction servers. The second approach made use of the information on the secondary structures extracted from structure prediction servers, threading techniques and DSSP database of some of the templates used in the threading techniques. Consensus on the one-dimensional secondary structure of Den2 protease was obtained from each approach and evaluated against data from the recently crystallised Den2 NS2B/NS3 obtained from the Protein Data Bank (PDB). Results indicated the second approach to show higher accuracy compared to the use of prediction servers only. Thus, it is plausible that this approach is applicable to the initial stage of structural studies of proteins with low amino acid sequence homology against other available proteins in the PDB.
  12. 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
    Osman H, Idris NH, Kamarulzaman EE, Wahab HA, Hassan MZ
    Acta Pharm Sin B, 2017 Jul;7(4):479-484.
    PMID: 28752033 DOI: 10.1016/j.apsb.2017.04.009
    Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a-4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 µmol/L.
  13. Fulltext Assessing the potential of NS2B/NS3 protease inhibitors biomarker in curbing dengue virus infections: In silico vs. In vitro approach
    Norshidah H, Leow CH, Ezleen KE, Wahab HA, Vignesh R, Rasul A, et al.
    Front Cell Infect Microbiol, 2023;13:1061937.
    PMID: 36864886 DOI: 10.3389/fcimb.2023.1061937
    An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia® vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involving in silico screening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from the in silico and in vitro perspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area.
  14. Public Health Services for Foreign Workers in Malaysia
    Noh NA, Wahab HA, Bakar Ah SH, Islam MR
    Soc Work Public Health, 2016 Aug-Sep;31(5):419-30.
    PMID: 27177326 DOI: 10.1080/19371918.2015.1125321
    The objective of this study was to know the status of the foreign workers' access to public health services in Malaysia based on their utilization pattern. The utilization pattern covered a number of areas, such as frequency of using health services, status of using health services, choice and types of health institutions, and cost of health treatment. The study was conducted on six government hospitals in the Klang Valley area in Kuala Lumpur, Malaysia. Data were collected from 600 foreign patients working in the country, using an interview method with a structured questionnaire. The results showed that the foreign workers' access to public health services was very low. The findings would be an important guideline to formulate an effective health service policy for the foreign workers in Malaysia.
  15. Fulltext Potential activity of fevicordin-A from Phaleria macrocarpa (Scheff) Boerl. seeds as estrogen receptor antagonist based on cytotoxicity and molecular modelling studies
    Muchtaridi M, Yusuf M, Diantini A, Choi SB, Al-Najjar BO, Manurung JV, et al.
    Int J Mol Sci, 2014 Apr 25;15(5):7225-49.
    PMID: 24776765 DOI: 10.3390/ijms15057225
    Fevicordin-A (FevA) isolated from Phaleria macrocarpa (Scheff) Boerl. seeds was evaluated for its potential anticancer activity by in vitro and in silico approaches. Cytotoxicity studies indicated that FevA was selective against cell lines of human breast adenocarcinoma (MCF-7) with an IC50 value of 6.4 µM. At 11.2 µM, FevA resulted in 76.8% cell death of T-47D human breast cancer cell lines. Critical pharmacophore features amongst human Estrogen Receptor-α (hERα) antagonists were conserved in FevA with regard to a hypothesis that they could make notable contributions to its pharmacological activity. The binding stability as well as the dynamic behavior of FevA towards the hERα receptor in agonist and antagonist binding sites were probed using molecular dynamics (MD) simulation approach. Analysis of MD simulation suggested that the tail of FevA was accountable for the repulsion of the C-terminal of Helix-11 (H11) in both agonist and antagonist receptor forms. The flexibility of loop-534 indicated the ability to disrupt the hydrogen bond zipper network between H3 and H11 in hERα. In addition, MM/GBSA calculation from the molecular dynamic simulations also revealed a stronger binding affinity of FevA in antagonistic action as compared to that of agonistic action. Collectively, both the experimental and computational results indicated that FevA has potential as a candidate for an anticancer agent, which is worth promoting for further preclinical evaluation.
  16. Fulltext Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound
    Muchtaridi M, Lestari D, Khairul Ikram NK, Gazzali AM, Hariono M, Wahab HA
    Molecules, 2021 Jun 04;26(11).
    PMID: 34199752 DOI: 10.3390/molecules26113402
    Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson's, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 μg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.
  17. Fulltext Neuraminidase Inhibitor of Garcinia atroviridis L. Fruits and Leaves Using Partial Purification and Molecular Characterization
    Muchtaridi M, Nuwarda RF, Ikram EHK, Abdul Rahim AS, Gazzali AM, Wahab HA
    Molecules, 2022 Jan 30;27(3).
    PMID: 35164214 DOI: 10.3390/molecules27030949
    Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.
  18. Fulltext Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2
    Muchtaridi M, Fauzi M, Khairul Ikram NK, Mohd Gazzali A, Wahab HA
    Molecules, 2020 Sep 01;25(17).
    PMID: 32882868 DOI: 10.3390/molecules25173980
    Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.
  19. Fulltext Advanced Nanoparticle-Based Drug Delivery Systems and Their Cellular Evaluation for Non-Small Cell Lung Cancer Treatment
    Mohtar N, Parumasivam T, Gazzali AM, Tan CS, Tan ML, Othman R, et al.
    Cancers (Basel), 2021 Jul 15;13(14).
    PMID: 34298753 DOI: 10.3390/cancers13143539
    Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.
  20. Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients
    Mohseni J, Al-Najjar BO, Wahab HA, Zabidi-Hussin ZA, Sasongko TH
    J Hum Genet, 2016 Sep;61(9):823-30.
    PMID: 27251006 DOI: 10.1038/jhg.2016.61
    Several histone deacetylase inhibitors (HDACis) are known to increase Survival Motor Neuron 2 (SMN2) expression for the therapy of spinal muscular atrophy (SMA). We aimed to compare the effects of suberoylanilide hydroxamic acid (SAHA) and Dacinostat, a novel HDACi, on SMN2 expression and to elucidate their acetylation effects on the methylation of the SMN2. Cell-based assays using type I and type II SMA fibroblasts examined changes in transcript expressions, methylation levels and protein expressions. In silico methods analyzed the intermolecular interactions between each compound and HDAC2/HDAC7. SMN2 mRNA transcript levels and SMN protein levels showed notable increases in both cell types, except for Dacinostat exposure on type II cells. However, combined compound exposures showed less pronounced increase in SMN2 transcript and SMN protein level. Acetylation effects of SAHA and Dacinostat promoted demethylation of the SMN2 promoter. The in silico analyses revealed identical binding sites for both compounds in HDACs, which could explain the limited effects of the combined exposure. With the exception on the effect of Dacinostat in Type II cells, we have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene.
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