Synthesis, Anticancer Evaluation and in Silico Studies of 1,4-Dihydropyridines.

An efficient 1,4-dihydropyridine synthesis under mild conditions has been developed. Numerous substrates were tested, with yields of 1,4-dihydropridines ranging from good to excellent and a wide range of functional group tolerance. A549, HT-29, and HepG2 cancer cells were used to investigate the anticancer efficacy of each of the produced compounds. Additionally, in-silico docking studies were conducted to understand the structure-based features of the anticancer mechanism with the cancer medication target of Adenosine A2A receptor as well as the molecular level interactions of the compounds.

C-Dimethylated Flavones as Possible Potential Anti-Tubercular and Anticancer Agents.

The present investigation describes an intramolecular Oxa-Michael addition of penta-substituted phenols to the enone of the tether in the presence of iodine as the oxidizing agent. Ten C-Dimethylated flavones with moderate to good yields (10a-j, 60-89 %) were isolated by heating the corresponding C-dimethylated chalcones using iodine in DMSO. Using the Microplate Alamar Blue test (MABA) technique, the drugs' quantitative drug susceptibility against the H37Rv strain of replicating Mycobacterium TB was determined. The sensitivity of two of the developed compounds (10e, 10h) was up to 6.25 g/mL. The human lung adenocarcinoma cell lines (A549) were used in the anticancer study, which was carried out using the MTT cell proliferation assay. In A549 cell lines, four flavones demonstrated anticancer activity with IC50 values between 39 and 48 µM. The C-dimethylated flavones, 10b (3,4-dimethoxy), 10c (2,3,4-trimethoxy), 10e (p-fluoro) and 10g (N-methyl indole) substitutions on ring 'B' showed good anticancer activity with IC50 values 39.17, 39.21, 48.43 and 43.48 µM, respectively. The compounds 10b, 10c, 10d, 10e, and 10i had improved binding and interaction profiles among all the compounds examined during the current In Silico research, as shown by the docking simulations against two targets EGFR and MTB MurI.

Copper-Promoted One-Pot Approach: Synthesis of Benzimidazoles.

A facile, one-pot, and proficient method was developed for the production of various 2-arylaminobenzimidazoles. This methodology is based for the first time on a copper catalyst promoted domino C-N cross-coupling reaction for the generation of 2-arylaminobenzimidazoles. Mechanistic investigations revealed that the synthetic pathway involves a copper-based desulphurization/nucleophilic substitution and a subsequent domino intra and intermolecular C-N cross-coupling reactions. Some of the issues typically encountered during the synthesis of 2-arylaminobezimidazoles, including the use of expensive catalytic systems and the low reactivity of bromo precursors, were addressed using this newly developed copper-catalyzed method. The reaction procedure is simple, generally with excellent substrate tolerance, and provides good to high yields of the desired products.

Copper-catalyzed synthesis of 2-aminophenyl benzothiazoles: a novel approach.

A novel, convenient and efficient protocol for the construction of various 2-aminophenyl benzothiazoles by domino intra- and intermolecular C-N cross-coupling reactions of arylisothioureas with aryl iodides using an inexpensive, air stable and readily available copper catalyst is described. The arylisothioureas were obtained from thiourea via copper promoted desulfurization followed by nucleophilic substitution. In addition, the reactivity of arylhalides and the reaction mechanism have also been studied. The protocol features operational simplicity and a broad substrate scope.

Ethyl Gallate: Promising Cytoprotective against HIV-1-Induced Cytopathy and Antiretroviral-Induced Cytotoxicity.

Introduction: HIV-1 infection in cell culture is typically characterized by certain cytopathic effects such as vacuolization of cells and development of syncytia, which further lead to cell death. In addition, the majority of drugs during HIV treatment exhibit serious adverse effects in patients, apart from their beneficial role. During the screening of cytoprotective agents to protect the cells from HIV-1-associated cell death and also drug-associated toxicity, antioxidants from a natural source are assumed to be a choice. A well-known antioxidant, ethyl gallate (EG), was selected for cytoprotection studies which have already been proven as an anti-HIV agent. Objective: The main objective of the study was to explore the cytoprotective potential of EG against HIV-1-induced cytopathic effect and antiretroviral drug toxicity. Methods: DPPH free radical scavenging assay was performed with EG to find the effective concentration for antioxidant activity. HIV-1infection-associated cytopathic effects and further rescue by EG were studied in MT-2 lymphocytes by the microscopic method and XTT cytopathic assays. The cellular toxicity of different antiretroviral drugs in different cell lines and the consequent cytoprotective effectiveness of EG were investigated using an MTT cell viability assay. Results: Like ascorbic acid, EG exhibited promising antioxidant activity. HIV-1 infection of MT2 cells induces cell death often referred to as the cytopathic effect. In addition, the usage of antiretroviral drugs also causes severe adverse effects like cytotoxicity. In this context, EG was tested for its cytoprotective properties against HIV-1-induced cytopathic effect and drug-mediated cellular toxicity. EG reclaimed back the MT2 cells from HIV-1-induced cell death. Antiretroviral drugs, such as ritonavir, efavirinz, AZT, and nevirapine, were tested for their toxicity and induced more cell death at higher concentrations in different tissue models such as the liver (THLE-3), lung (AEpiCM), colorectal (HT-29), and brain (U87 MG). Pretreated cells with EG were rescued from the toxic doses of ART. Conclusion: EG was found to be exhibited cytoprotection not only from HIV-1-linked cell death but also from the chemotoxicity of antiretroviral drugs. Evidently, EG could be a cytoprotective supplement in the management of AIDS along with its enormous antioxidant benefits.

Synthesis of Pharmacological Relevant 1,2,3-Triazole and Its Analogues-A Review.

In this review, authors focus mostly on the various synthetic strategies developed so far for 1,2,3- triazole scaffold and its derivatives via different approaches such as metal-free, metal assisted or bimetallic. A brief overview of applications of the very important 1,2,3-triazole scaffold along with pharmacological activity is also discussed. Synthetic strategies are updated until June 2020.

A Mini Review on Emerging Targets and Approaches for the Synthesis of Anti-viral Compounds: In Perspective to COVID-19.

The novel Coronavirus disease (COVID-19) is an epidemic disease that appeared at the end of the year 2019 with a sudden increase in number and came to be considered as a pandemic disease caused by a viral infection which has threatened most countries for an emergency search for new anti-SARS-COV drugs /vaccines. At present, the number of clinical trials is ongoing worldwide on different drugs i.e. Hydroxychloroquine, Remedisvir, Favipiravir that utilize various mechanisms of action. A few countries are currently processing clinical trials, which may result in a positive outcome. Favipiravir (FPV) represents one of the feasible treatment options for COVID-19, if the result of the trials turns out positive. Favipiravir will be one of the developed possibly authoritative drugs to warrant benefits to mankind with large-scale production to meet the demands of the current pandemic Covid-19 outbreak and future epidemic outbreaks. In this review, the authors tried to explore key molecules, which will be supportive for devising COVID-19 research.

An efficient approach for the synthesis of novel methyl sulfones in acetic acid medium and evaluation of antimicrobial activity.

A series of nine methyl sulphones ( 3a -3 i ) starting from the aldehydes ( 1a-1i ) were synthesized in two consecutive steps. In the first step, preparation of allyl alcohols ( 2a-2i ) from their corresponding aldehydes by the reaction of sodium borohydride in methanol at room temperature is reported. Finally, methyl sulphones are synthesized by condensing sodium methyl sulfinates with allyl alcohols in the presence of BF 3 .Et 2 O in acetic acid medium at room temperature for about 2-3 h. The reaction conditions are simple, yields are high (85%-95%), and the products were obtained with good purity. All the synthesized compounds were characterized by their 1 H, 13 C NMR, and mass spectral analysis. All the title compounds were screened for antimicrobial activity. Among the compounds tested, the compound 3f has inhibited both Gram positive and Gram negative bacteria effectively and compound 3i has shown potent antifungal activity. These promising components may help to develop more potent drugs in the near future for the treatment of bacterial and fungal infections.