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  1. Fulltext Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties
    Veligeti R, Madhu RB, Anireddy J, Pasupuleti VR, Avula VKR, Ethiraj KS, et al.
    Sci Rep, 2020 11 26;10(1):20720.
    PMID: 33244007 DOI: 10.1038/s41598-020-77590-1
    Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand-protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from - 8.1394 to - 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry*
  2. Fulltext Phytochemistry, Traditional Use and Pharmacological Activity of Picrasma quassioides: A Critical Reviews
    Mohd Jamil MDH, Taher M, Susanti D, Rahman MA, Zakaria ZA
    Nutrients, 2020 Aug 26;12(9).
    PMID: 32858812 DOI: 10.3390/nu12092584
    Picrasma quassioides is a member of the Simaroubaceae family commonly grown in the regions of Asia, the Himalayas, and India and has been used as a traditional herbal medicine to treat various illnesses such as fever, gastric discomfort, and pediculosis. This study aims to critically review the presence of phytochemicals in P. quassioides and correlate their pharmacological activities with the significance of its use as traditional medicine. Data were collected by reviewing numerous scientific articles from several journal databases on the pharmacological activities of P. quassioides using certain keywords. As a result, approximately 94 phytochemicals extracted from P. quassioides were found to be associated with quassinoids, β-carbolines and canthinones. These molecules exhibited various pharmacological benefits such as anti-inflammatory, antioxidant, anti-cancer, anti-microbial, and anti-parasitic activities which help to treat different diseases. However, P. quassioides were also found to have several toxicity effects in high doses, although the evidence regarding these effects is limited in proving its safe use and efficacy as herbal medicine. Accordingly, while it can be concluded that P. quassioides may have many potential pharmacological benefits with more phytochemistry discoveries, further research is required to determine its real value in terms of quality, safety, and efficacy of use.
    Matched MeSH terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use
  3. Potential CD34 signaling through phosphorylated-BAD in chemotherapy-resistant acute myeloid leukemia
    Yiau SK, Lee C, Mohd Tohit ER, Chang KM, Abdullah M
    J Recept Signal Transduct Res, 2019 Jun;39(3):276-282.
    PMID: 31509041 DOI: 10.1080/10799893.2019.1660899
    Acute myeloid leukemia (AML) constitutively express growth factors and cytokines for survival. Chemotherapy alters these signals to induce cell death. However, drug resistance in AML remains a major hindrance to successful treatment and early warning is unavailable. Modulation of signaling pathways during chemotherapy may provide a window to detect response and predict treatment outcome. Blood samples collected from AML patients before and at day-3 of induction therapy were compared for changes in expression of CD117, CD34, pro-inflammatory cytokines and mediators of Akt and MAPK pathways, using multi-color flow cytometry. Nine patients were diagnosed as drug-resistant and seven sensitive to chemotherapy. Twelve were paired. Average percentages of CD34 (66.8 ± 11.7% vs. 26.2 ± 5.8%, p = 0.033) and pBAD (66.9 ± 8.2% vs. 28.9 ± 8.2%, p = 0.016) were significantly increased in chemo-resistant (N = 9) compared to chemo-sensitive (N = 5) samples. Percentages of CD34 were strongly correlated with pBAD (R = 0.785; p = 0.001; N = 14) and pFKHR (R = 0.755; p = 0.002; N = 14) at day-3 induction. Chemo-sensitive cases expressed significantly higher percentages of IL-18Rα (71.9 ± 9.6% vs. 29.8 ± 5.8%, p = 0.016). Though not significantly different in the outcome, IL-1β was strongly associated with activated Akt-S473, IL-6 with phosphorylated JNK and FKHR while TNF-α appeared to trigger Bim, in treated samples. These preliminary results suggested AML cells resistant to chemotherapy increased expression of CD34 and may signal through pBAD while cells sensitive to chemotherapy-induced IL18Rα expression. These were observed early during induction therapy. Identifying CD34 is interesting as it is a convenient marker to monitor drug-resistance in AML patients. Inhibition of CD34 and pBAD signaling may be important in treating drug-resistant AML.
    Matched MeSH terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use*
  4. Triphenyltin(IV) benzoates with diazenyl/imino scaffold exhibiting remarkable apoptosis mediated by reactive oxygen species
    Basu Baul TS, Dutta D, Duthie A, Prasad R, Rana NK, Koch B, et al.
    J Inorg Biochem, 2017 08;173:79-92.
    PMID: 28505480 DOI: 10.1016/j.jinorgbio.2017.04.020
    The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(Ln)] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where Ln=L1-3; isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L4-6are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR (1H,13C,119Sn) techniques. The molecular structures of a pro-ligand 2-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoic acid (HL4) and two representative molecules, Ph3Sn(L2) 2 and Ph3Sn(L5) 5, have been determined by X-ray crystallography. Structural analyses of 2 and 5 revealed distorted tetrahedral geometries within C3O donor sets owing to monodentate modes of coordination of the respective carboxylate ligands, close intramolecular Sn…O(carbonyl) interactions notwithstanding. Cytotoxic studies in vitro in MDA-MB-231 and HeLa cell lines revealed high activity, in sub-micromolar range, for all investigated compounds. Among these, 1 and 3 exhibited potent cytotoxicity most effectively towards MDA-MB-231 cells with a IC50value of 1.19 and 1.44μM, respectively, whereas 5 showed remarkable activity towards HeLa cells with a IC50value of 0.88μM, yet the series of compounds had minimal cytotoxic effect on normal HEK 293 (human embryonic kidney) cell line. The underlying investigation suggested that the compounds exert potent antitumor effect by elevating intracellular reactive oxygen species generation and cause delay in cell cycle by inhibiting cells at G2/M phase. The results presented herein suggest further development of this class of triphenyltin(IV) compounds-based drugs as potential anti-cancer therapies should be pursued.
    Matched MeSH terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry
  5. Fulltext Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells
    Huang TT, Lan YW, Chen CM, Ko YF, Ojcius DM, Martel J, et al.
    Sci Rep, 2019 03 26;9(1):5145.
    PMID: 30914735 DOI: 10.1038/s41598-019-41653-9
    We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Antineoplastic Agents, Phytogenic/chemistry
  6. The Potential Use of Anticancer Peptides (ACPs) in the Treatment of Hepatocellular Carcinoma
    Ng CX, Lee SH
    Curr Cancer Drug Targets, 2020;20(3):187-196.
    PMID: 31713495 DOI: 10.2174/1568009619666191111141032
    Peptides have acquired increasing interest as promising therapeutics, particularly as anticancer alternatives during recent years. They have been reported to demonstrate incredible anticancer potentials due to their low manufacturing cost, ease of synthesis and great specificity and selectivity. Hepatocellular carcinoma (HCC) is among the leading cause of cancer death globally, and the effectiveness of current liver treatment has turned out to be a critical issue in treating the disease efficiently. Hence, new interventions are being explored for the treatment of hepatocellular carcinoma. Anticancer peptides (ACPs) were first identified as part of the innate immune system of living organisms, demonstrating promising activity against infectious diseases. Differentiated beyond the traditional effort on endogenous human peptides, the discovery of peptide drugs has evolved to rely more on isolation from other natural sources or through the medicinal chemistry approach. Up to the present time, the pharmaceutical industry intends to conduct more clinical trials for the development of peptides as alternative therapy since peptides possess numerous advantages such as high selectivity and efficacy against cancers over normal tissues, as well as a broad spectrum of anticancer activity. In this review, we present an overview of the literature concerning peptide's physicochemical properties and describe the contemporary status of several anticancer peptides currently engaged in clinical trials for the treatment of hepatocellular carcinoma.
    Matched MeSH terms: Antineoplastic Agents/therapeutic use*; Antineoplastic Agents/chemistry
  7. Hibiscus cannabinus L. (kenaf) studies: Nutritional composition, phytochemistry, pharmacology, and potential applications
    Sim YY, Nyam KL
    Food Chem, 2021 May 15;344:128582.
    PMID: 33199120 DOI: 10.1016/j.foodchem.2020.128582
    The electronic database was searched up to July 2020, using keywords, kenaf and roselle, chemical constituents of kenaf and roselle, therapeutic uses of kenaf and roselle. Journals, books and conference proceedings were also searched. Investigations of pharmacological activities of kenaf revealed that this edible plant exhibits a broad range of therapeutic potential including antioxidant, antimicrobial, antityrosinase, anticancer, antihyperlipidemia, antiulcer, anti-inflammatory, and hepatoprotective activities. Kenaf also showed versatile utility as a functional ingredient in food, folk medicine, and animal nutritions, as well as in nanotechnology processes. The exploitation of underexploited kenaf by-products can be a significant part of waste management from an economic and environmental point of view. In addition, kenaf showed comparable nutritional, phytochemical, and pharmacological properties with Hibiscus sabdariffa (Roselle). This review has important implications for further investigations and applications of kenaf in food and pharmaceuticals industry.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/chemistry
  8. The influence of genetic polymorphisms on the efficacy and side effects of anastrozole in postmenopausal breast cancer patients
    Abubakar MB, Wei K, Gan SH
    Pharmacogenet Genomics, 2014 Dec;24(12):575-81.
    PMID: 25203739 DOI: 10.1097/FPC.0000000000000092
    Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemestane)] is used as an alternative to tamoxifen or following several years of tamoxifen treatment. Nevertheless, this approach is still associated with many challenges, ranging from the recurrence of breast cancer to considerable interindividual variability in the tolerability of anastrozole, which may cause adverse effects, such as musculoskeletal symptoms, and lead to the withdrawal of many patients from treatment. Variabilities in the genes encoding the drug target (aromatase) or its metabolizing enzymes (CYP3A and UGT1A) contribute toward the interindividual variability in anastrozole's pharmacokinetics and/or pharmacodynamics. This paper reviews the role of genetic polymorphisms of CYP19A1, CYP3A4, and UGT1A4 in the responses of female hormone receptor-positive postmenopausal breast cancer patients to anastrozole. Many reviews in the literature have suggested that the study of functional polymorphisms and investigation of relevant genetic markers may provide valuable information in predicting responses to anastrozole in terms of its therapeutic and adverse effects. Nevertheless, more studies are required before the knowledge of its pharmacogenomics can be applied to the individualization of treatment to ensure that patients receive the maximum benefits. Therefore, future analyses, including but not limited to genome-wide association studies, are encouraged to address some of the gray areas in the pharmacogenomics of anastrozole therapy in postmenopausal breast cancer cases; this will help in providing guidance for future pharmacogenomics protocols when anastrozole is utilized in patients' management.
    Matched MeSH terms: Antineoplastic Agents, Hormonal/adverse effects; Antineoplastic Agents, Hormonal/pharmacokinetics*
  9. Fulltext Mangrove derived Streptomyces sp. MUM265 as a potential source of antioxidant and anticolon-cancer agents
    Tan LT, Chan KG, Pusparajah P, Yin WF, Khan TM, Lee LH, et al.
    BMC Microbiol, 2019 02 13;19(1):38.
    PMID: 30760201 DOI: 10.1186/s12866-019-1409-7
    BACKGROUND: Colon cancer is the third most commonly diagnosed cancer worldwide, with a commensurately high mortality rate. The search for novel antioxidants and specific anticancer agents which may inhibit, delay or reverse the development of colon cancer is thus an area of great interest; Streptomyces bacteria have been demonstrated to be a source of such agents.

    RESULTS: The extract from Streptomyces sp. MUM265- a strain which was isolated and identified from Kuala Selangor mangrove forest, Selangor, Malaysia- was analyzed and found to exhibit antioxidant properties as demonstrated via metal-chelating ability as well as superoxide anion, DPPH and ABTS radical scavenging activities. This study also showed that MUM265 extract demonstrated cytotoxicity against colon cancer cells as evidenced by the reduced cell viability of Caco-2 cell line. Treatment with MUM265 extract induced depolarization of mitochondrial membrane potential and accumulation of subG1 cells in cell cycle analysis, suggesting that MUM265 exerted apoptosis-inducing effects on Caco-2 cells.

    CONCLUSION: These findings indicate that mangrove derived Streptomyces sp. MUM265 represents a valuable bioresource of bioactive compounds for the future development of chemopreventive agents, with particular promise suggested for treatment of colon cancer.

    Matched MeSH terms: Antineoplastic Agents/isolation & purification; Antineoplastic Agents/pharmacology*
  10. A case of iatrogenic Cushing syndrome and apparent mineralocorticoid excess presenting with accelerated hypertension and proteinuria
    Kong WY, Leedman P, Irish A
    Intern Med J, 2014 Sep;44(9):932-4.
    PMID: 25201428 DOI: 10.1111/imj.12022
    Matched MeSH terms: Antineoplastic Agents, Hormonal/administration & dosage; Antineoplastic Agents, Hormonal/adverse effects*
  11. Fulltext Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs
    Kue CS, Tan KY, Lam ML, Lee HB
    Exp Anim, 2015;64(2):129-38.
    PMID: 25736707 DOI: 10.1538/expanim.14-0059
    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage; Antineoplastic Agents/toxicity*
  12. Biocompatible Ionic Liquid-Mediated Micelles for Enhanced Transdermal Delivery of Paclitaxel
    Ali MK, Moshikur RM, Wakabayashi R, Moniruzzaman M, Goto M
    ACS Appl Mater Interfaces, 2021 May 05;13(17):19745-19755.
    PMID: 33891816 DOI: 10.1021/acsami.1c03111
    Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-π and π-π interactions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/administration & dosage*; Antineoplastic Agents, Phytogenic/pharmacokinetics
  13. Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP-T1 cells
    Lu MC, Li TY, Hsieh YC, Hsieh PC, Chu YL
    Environ Toxicol, 2018 Dec;33(12):1229-1236.
    PMID: 30188005 DOI: 10.1002/tox.22629
    Clinacanthus nutans has been used as herbal medicine with antidiabetic, blood pressure lowering, and diuretic properties in Singapore, Thailand, and Malaysia. The in vitro cellular study showed the chloroform extract possessed significant cytotoxicity against leukemia K562 and lymphoma Raji cells. The clinical study reported that administration of plant could treat or prevent relapse in 12 cancer patients. However, detailed mechanism of the anticancer effects and chemical profiles are not thoroughly studied. The chemical study did show that the acetone extract (MHA) exerted the highest antiproliferative effect on human leukemia MOLT-4 cells and lymphoma SUP-T1 cells in dose-dependent cytotoxicity. We found that the use of MHA increased apoptosis by 4.28%-43.65% and caused disruption of mitochondrial membrane potential (MMP) by 11.79%-26.93%, increased reactive oxygen species (ROS) by 19.54% and increased calcium ion by 233.83%, as demonstrated by annexin-V/PI, JC-1, H2 DCFDA, and Flou-3 staining assays, respectively. MHA-induced ER stress was confirmed by increase expression of CHOP and IRE-1α with western blotting assay. In conclusion, we identified good bioactivity in Clinacanthus nutans and recognize its potential effect on cancer therapy, but further research is needed to determine the use of the plant.
    Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/chemistry
  14. Peroxiredoxin of Arthrospira platensis derived short molecule YT12 influences antioxidant and anticancer activity
    Sannasimuthu A, Ramani M, Pasupuleti M, Saraswathi NT, Arasu MV, Al-Dhabi NA, et al.
    Cell Biol Int, 2020 Nov;44(11):2231-2242.
    PMID: 32716104 DOI: 10.1002/cbin.11431
    This study demonstrates both the antioxidant and anticancer potential of the novel short molecule YT12 derived from peroxiredoxin (Prx) of spirulina, Arthrospira platensis (Ap). ApPrx showed significant reduction in reactive oxygen species (ROS) against hydrogen peroxide (H2 O2 ) stress. The complementary DNA sequence of ApPrx contained 706 nucleotides and its coding region possessed 546 nucleotides between position 115 and 660. Real-time quantitative reverse transcription polymerase chain reaction analysis confirmed the messenger RNA expression of ApPrx due to H2 O2 exposure in spirulina cells at regular intervals, in which the highest expression was noticed on Day 20. Cytotoxicity assay was performed using human peripheral blood mononuclear cells, and revealed that at 10 μM, the YT12 did not exhibit any notable toxicity. Furthermore, ROS scavenging activity of YT12 was performed using DCF-DA assay, in which YT12 scavenged a significant amount of ROS at 25 μM in H2 O2 -treated blood leukocytes. The intracellular ROS in human colon adenocarcinoma cells (HT-29) was regulated by oxidative stress, where the YT12 scavenges ROS in HT-29 cells at 12.5 μM. Findings show that YT12 peptide has anticancer activity, when treated against HT-29 cells. Through the MTT assay, YT12 showed vital cytotoxicity against HT-29 cells. These finding suggested that YT12 is a potent antioxidant molecule which defends ROS against oxidative stress and plays a role in redox balance.
    Matched MeSH terms: Antineoplastic Agents/metabolism; Antineoplastic Agents/pharmacology
  15. Potential anticancer activity of protocatechuic acid loaded in montmorillonite/Fe3O4 nanocomposites stabilized by seaweed Kappaphycus alvarezii
    Yew YP, Shameli K, Mohamad SEB, Nagao Y, Teow SY, Lee KX, et al.
    Int J Pharm, 2019 Dec 15;572:118743.
    PMID: 31705969 DOI: 10.1016/j.ijpharm.2019.118743
    Superparamagnetic magnetite nanocomposites (Fe3O4-NCs) were successfully synthesized, which comprised of montmorillonite (MMT) as matrix support, Kappaphycus alvarezii (SW) as bio-stabilizer and Fe3O4 as filler in the composites to form MMT/SW/Fe3O4-NCs. Nanocomposite with 0.5 g Fe3O4 (MMT/SW/0.5Fe3O4) was selected for anticancer activity study because it revealed high crystallinity, particle size of 7.2 ± 1.7 nm with majority of spherical shape, and Ms = 5.85 emu/g with negligible coercivity. Drug loading and release studies were carried out using protocatechuic acid (PCA) as the model for anticancer drug, which showed 19% and 87% of PCA release in pH 7.4 and 4.8, respectively. Monolayer anticancer assay showed that PCA-loaded MMT/SW/Fe3O4 (MMT/SW/Fe3O4-PCA) had selectivity towards HCT116 (colorectal cancer cell line). Although MMT/SW/Fe3O4-PCA (0.64 mg/mL) showed higher IC50 than PCA (0.148 mg/mL) and MMT/SW/Fe3O4 (0.306 mg/mL, MMT/SW/Fe3O4-PCA showed more effective killing towards tumour spheroid model generated from HCT116. The IC50 for MMT/SW/Fe3O4-PCA, MMT/SW/Fe3O4 and PCA were 0.132, 0.23 and 0.55 mg/mL, respectively. This suggests the improved penetration efficiency and drug release of MMT/SW/Fe3O4-PCA towards HCT116 spheroids. Moreover, concentration that lower than 2 mg/mL MMT/SW/Fe3O4-PCA did not result any hemolysis in human blood, which suggests them to be ideal for intravenous injection. This study highlights the potential of MMT/SW/Fe3O4-NCs as drug delivery agent.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry
  16. Preparation and characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability
    Kiew SF, Ho YT, Kiew LV, Kah JCY, Lee HB, Imae T, et al.
    Int J Pharm, 2017 Dec 20;534(1-2):297-307.
    PMID: 29080707 DOI: 10.1016/j.ijpharm.2017.10.045
    We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO100-DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, α-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of α-amylase to simulate tumor conditions, GO100-DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO100. Under the same conditions, the cytotoxic effects of GO100-DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO100/DOX. Employing an in vitro biomimetic microfluidic blood vessel model lined with human umbilical vein endothelial cells, we evaluated the tumor vasculature endothelial permeation of GO100-DEX and GO100 using dextrans of 10 and 70kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO100-DEX and GO100 were 4.3- and 4.9-fold greater than that of 70kDa dextran and 2.7- and 3.1-fold higher than that of 10kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier.
    Matched MeSH terms: Antineoplastic Agents/metabolism; Antineoplastic Agents/chemistry*
  17. Theranostic application of nanoemulsions in chemotherapy
    Gorain B, Choudhury H, Nair AB, Dubey SK, Kesharwani P
    Drug Discov Today, 2020 07;25(7):1174-1188.
    PMID: 32344042 DOI: 10.1016/j.drudis.2020.04.013
    Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.
    Matched MeSH terms: Antineoplastic Agents/pharmacology*; Antineoplastic Agents/therapeutic use*
  18. Hybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review
    Prasher P, Sharma M, Aljabali AAA, Gupta G, Negi P, Kapoor DN, et al.
    Drug Dev Res, 2020 11;81(7):837-858.
    PMID: 32579723 DOI: 10.1002/ddr.21704
    Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
    Matched MeSH terms: Antineoplastic Agents/therapeutic use; Antineoplastic Agents/chemistry
  19. Mucoadhesive Chitosan-Pectinate Nanoparticles for the Delivery of Curcumin to the Colon
    Alkhader E, Billa N, Roberts CJ
    AAPS PharmSciTech, 2017 May;18(4):1009-1018.
    PMID: 27582072 DOI: 10.1208/s12249-016-0623-y
    In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage; Antineoplastic Agents/pharmacokinetics
  20. Dendrimer nanoarchitectures for cancer diagnosis and anticancer drug delivery
    Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U
    Drug Discov Today, 2017 02;22(2):314-326.
    PMID: 27671487 DOI: 10.1016/j.drudis.2016.09.013
    Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/therapeutic use
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