BackgroundBenzimidazoles and triazoles are useful structures for research and development of new pharmaceutical molecules and have received much attention in the last decade because of their highly potent medicinal activities.FindingsA simple and efficient synthesis of triazole was carried out by treatment of 2-(4-azidophenyl)-1H-benzo[d]imidazole (6) with different types of terminal alkynes in t-BuOH/H2O, sodium ascorbate, and Zn(OTf)2, screened for cytotoxicity assay and achieved good results. A series of new benzimidazole-linked 1,2,3-triazole (8a-i) congeners were synthesized through cyclization of terminal alkynes and azide. These synthesized congeners 8a-i were evaluated for their cytotoxicity against five human cancer cell lines. These benzimidazole-linked 1,2,3-triazole derivatives have shown promising activity with IC50 values ranging from 0.1 to 43 μM. Among them, the compounds (8a, 8b, 8c, and 8e) showed comparable cytotoxicity with adriamycin control drug.ConclusionsIn conclusion, we have developed a simple, convenient, and an efficient convergent approach for the synthesis of benzimidazole-linked 1,2,3-triazole congeners as agents.Graphical AbstractSynthesis of 1,2,3-triazole derivativesElectronic supplementary materialThe online version of this article (doi:10.1186/s13588-014-0014-x) contains supplementary material, which is available to authorized users.

A library of arylidenefuropyridinediones was discovered as potent inhibitors of Leishmania donovani Topoisomerase 1 (LdTop1) where the active molecules displayed considerable inhibition with single digit micromolar EC50 values. This molecular library was designed via intuitive scaffold hopping and bioisosteric modification of known topoisomerase 1 inhibitors such as camptothecin, edotecarin and etc. The design was rationalized by molecular docking analysis of the compound prototype with human topoisomerase 1 (HTop1) and Leishmania donovani topoisomerase 1(LdTop1). The most active compound 4 displayed no cytotoxicity against normal mammalian COS7 cell line (~100 fold less inhibition at the EC50). Similar to camptothecin, 4 interacted with free LdTop1 as observed in the preincubation DNA relaxation inhibition experiment. It also displayed anti-protozoal activity against Leishmania donovani promastigote. Crystal structure investigation of 4 and its molecular modelling with LdTop1 revealed putative binding sites in the enzyme that could be harnessed to generate molecules with better potency.

The global preponderance of diabetes mellitus has prompted the medical community to opt for various therapeutic solutions to curb the menace. One of the means involved controlling the post prandial hyperglycemia. α-glucosidase inhibitors are known to be excellent agents of controlling postprandial hyperglycemia. Different classes of α-glucosidase inhibitors has been discovered.In this context, a diverse library of substituted furopyridinediones (12a-v) was designed as potential inhibitors of α-glucosidase, using an intuitive scaffold hopping approach (which was further rationalized by molecular docking). They were synthesized in one step via an aldol condensation reaction of furopyridinedione scaffold and appropriate aldehydes. The compounds were screened against α-glucosidase using acarbose as the reference inhibitor. Among the screened compounds, 12p transpired to be the lead candidate with an IC 50 of 0.24 µM.Lineweaver Burke analysis of 12p indicated it to be a mixed inhibitor. X-ray crystallography of 12p further confirmed its structure. Molecular modelling studies and molecular dynamic simulation experiments were performed against a homology model of α-glucosidase to observe the binding interaction of 12p with the enzymes.

Michael addition of 2-aminopyridines with methylpropiolate to afforded the addition compound 1 a-g , which on further cyclisation at higher temperature in dowtherm-A to yield cyclised product 2 a-g , with respective yields depends on the nature of the substituents.Key words: Propionoic acid methyl ester, 2-aminopyridine and 3-(Pyridin-2-ylamino)-acrylic acid methyl ester.

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