Letters in Drug Design & Discovery - Volume 16, Issue 8, 2019

Background: None small cell cancer (NSCLC) is one of the most common cancer around the globe. First generation EGFR-TKI such as gefitinib and erlotinib are now documentated a prolonged PFS in NSCLC patients with EGFR activating mutation. However, upon continuous treatment, patients become resistant due toCEE T790M mutation in most cases.Second generation covalent EGFR inhibitors like afatinib have a moderate in Read More

Background: Diabetes mellitus is the third-largest non-communicable chronic disease worldwide. There are many effective drugs, but the long-term use of these clinical drugs may cause various side effects. Therefore, it is urgent to develop new antidiabetic molecules with higher efficacy and lower toxicity. Methods: Fifteen new 3-aryl-1-(5-methylisoxazol-3-ylamino)-1-(4-nitrophenyl)propan-1-one were synthesized directly throu Read More

Background: In an effort to establish new drug candidates with improved antiproliferative activity, we report here a novel class of compounds designed rationally by the replacement of an ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) and the introduction of 1,4- substituted 1,2,3-triazoles in the basic side chain. Methods: Magnetically separable iron oxide nanoparticles have been found to effectively catalyze t Read More

Background: Isocitrate dehydrogenase 2 (IDH2) is an enzyme catalyzing the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA). Evidences suggest that the specific mutations in IDH2 are critical to the growth and reproduction of severe tumors especially leukemia and glioblastoma. It is found that the inhibitors of mutant IDH2 are promising anti-tumor therapeutics. Methods: A vi Read More

Background: S-dihydro-alkyloxy-benzyl-oxopyrimidines (S-DABOs) as non-nucleoside reverse transcriptase inhibitors have received considerable attention during the last decade due to their high potency against HIV-1. Methods: In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) of a series of 38 S-DABO analogues developed in our lab was studied using Comparative Molecular Field Analysis Read More

Background: The drug-drug self-assembly was considered as a simple and efficient approach to prepare high drug loading nano-drug carriers and present new opportunities for cancer therapeutics. The strategy of PTX amphiphiles preparation would be a possible way to solve the poor water solubility of PTX. Methods: The PTX-YSL conjugate were synthesized and characterized. The PTX-YSL nanocarriers was prepared by a sim Read More

Background: Matrix metalloproteinase-9 (MMP-9) plays a crucial role in the development and progression of cancer. Therefore, identifying its inhibitors has enjoyed numerous attentions. In this report, a hybrid approach, including pharmacophore-based virtual screening, docking studies, and density functional theory (DFT) binding energy calculations followed by molecular dynamics simulations, was used to identify potenti Read More

Background: An extensive study of 19 pyrazole derivatives were carried out based on the evaluation of DNA cleavage properties, antimicrobial and cytotoxic activities and 4D-QSAR analysis including pharmacophore modelling and bioactivity prediction by the Electron Conformational-Genetic Algorithm (EC-GA) method. Methods: The pyrazole derivatives were tested for their antimicrobial activity against certain human pathoge Read More

Background: Hypertension is one of the key risk factors for cardiovascular disease, it is regulated through Renin Angiotensin Aldosterone System (RAAS) cascade. Renin catalyzes the initial rate-limiting step in RAAS system, that influences the synthesis of angiotensin I from precursor angiotensin. Renin inhibition could be a potential step for the blood pressure lowering mechanism as well as for organ protection. Metho Read More

Background: Benzimidazoles and its derivatives have been attracting interest for many years because of their biological activities. Benzimidazoles containing different heterocyclic moieties have wide range of biological activities such as antimicrobial, antioxidant, anticancer, antiviral, etc. Methods: In this study, some benzimidazole derivatives containing furan, oxadiazole, triazole and thiadiazole moieties have been synthes Read More

Background: Alternatives routes of delivery for Insulin have been evaluated to improve treatment for Diabetes Mellitus. The oral route is the most convenient physiologically; it releases in a similar way to endogenous secretion. Flexible liposomes have deformable abilities to pass through membranes with adequate therapeutic effects, but they have been tested only dermally. Objective: Our aim was to develop an oral nan Read More

Background: There is a great unmet medical need for new anticancer small molecule therapeutics. Exhaustive literature review suggests that benzothiazole derivatives have good potential to exhibit anticancer activity. Compounds that inhibit the kinase activity of EGFR are of potential interest as new antitumor agent. Objective: To design, synthesize and carry out in silico along with biological evaluation of 2- substituted Read More