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A series of twenty new 4-substituted-2,6-dimethyl-3,5-bis-N-(heteroaryl)-carbamoyl-1,4-dihydropyridines have been prepared from a three-component one-pot condensation reaction of N-heteroaryl acetoacetamide, an aromatic/heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco-friendly, economical, and the reactions were rapid and high-yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in-vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.

Pterostilbene is a naturally occurring dimethyl ether analog of resveratrol identified in several plant species. Telomerase is important in tumor initiation and cellular immortalization. Given the striking correlations between telomerase activity and proliferation capacity in tumor cells, telomerase had been considered as a potentially important molecular target in cancer therapeutics. Molecular docking studies were performed on pterostilbene with the crystal structure of telomerase (3DU6). Pterostilbene was evaluated for its in vitro cytotoxicity in breast (MCF7) and lung cancer (NCI H-460) cell lines, antimitotic activity in green grams and telomerase activity. Curcumin was used as a standard. Docking results indicated good interaction between pterostilbene and the active site of telomerase and the docked energy of pterostilbene was -7.10 kcal/mol. Pterostilbene showed strong inhibitory effect on in vitro telomerase activity and cell growth in both the cell lines tested in a dose dependent manner. Cancer cells treated with 80 µM pterostilbene exhibited significant telomerase inhibition, after 72 hours (MCF-7 and NCI H-460; 81.52% and 74.69% reduction, respectively, compared to control). The IC50 of pterostilbene for anti-proliferative activity in MCF7 and NCI H-460 cell lines were found to be 30.0 and 47.2 µM, respectively. The best antimitotic activity was obtained with 80 μM of pterostilbene (100% reduction in water imbibition). All the above results were comparable to that of curcumin. The drug-related properties of pterostilbene were calculated using Molinspiration, Osiris Property Explorer and ACD/Chemsketch softwares. Pterostilbene obeyed Lipinski's Rule of Five indicating its therapeutic potential in humans. It was found that the telomerase inhibitory activity exhibited by pterostilbene was dependent of the cell viability and has the potential to be a new drug candidate against breast and lung cancers.

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A series of new C 3 heterocyclic-substituted ciprofloxacin derivatives were prepared from ciprofloxacin acid hydrazide as possible chimeric molecules. They were evaluated for their possible in vitro antibacterial (agar cup/bore diffusion method) and antitubercular (Lowenstein-Jensen (LJ) slant method) activities. The results indicated that all the test compounds are highly effective against all the bacterial strains and have shown excellent anti-tubercular activity against normal, multidrug resistant and extensively drug resistant strains of Mycobacterium tuberculosis. They were found to be more potent antibacterial and antitubercular agents than the standard, ciprofloxacin. The minimum inhibitory concentration (MIC)'s of all the compounds against M. tuberculosis were found to be 0.0625 µg/mL as compared to ciprofloxacin (MIC 2 to > 8 µg/mL). Molecular docking studies were performed by using AUTODOCK 4.2 on the new ciprofloxacin derivatives at the active site of crystal structure of fluoroquinolones target enzyme Mtb DNA gyrase GyrA N-terminal domain (PDB ID: 3ILW) and also on the active site of crystal structure of chosen heterocyclics target enzyme enoyl-acyl carrier protein (ACP) reductase enzyme (PDB ID: 4TZK). Interestingly, almost all the compounds have shown relatively greater binding affinity at both the active sites than ciprofloxacin. Compound 6 exhibited the highest affinity for 3ILW and 4TZK.