V. Arun

A Facile Synthesis of Novel Bis‐(indolyl)‐1,3,4‐oxadiazoles as Potent Cytotoxic Agents

A recipe for potency: A novel series of bis(indolyl)-1,3,4-oxadiazoles was prepared from the corresponding hydrazide-hydrazones via iodobenzene diacetate-promoted oxidative cyclization. Evaluation against a panel of human cancer cell lines revealed that some derivatives possess potent cytotoxicity with tunable selectivity for different cancer types.

Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities.

A series of bis(indolyl)glyoxylamides 10a-n has been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole 9 with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides 10a-n in 82-93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human cancer cell lines. Of the screened analogues, compound 10f (IC50=22.34μM; HeLa, 24.05μM; PC-3, 21.13μM; MDA-MB-231 and 29.94μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either 10a or 10f resulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce apoptosis in PC-3 cells. Most importantly, compounds 10d, 10g and 10i were completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells.

Organohypervalent Iodine Reagents in the Synthesis of Bioactive Heterocycles

Facile and metal-free syntheses of natural and natural product-inspired bioactive heterocycles are of paramount importance in drug discovery program; therefore, it is highly desirable to develop efficient protocols to generate a diverse library of drug-like molecules. In recent years, organohypervalent iodines have played a vital role as eco-friendly recyclable reagents to construct a variety of bioactive heterocycles, particularly with five- and six-membered ring systems. Due to readily accessible, easy-to-use and shorter reaction times, organohypervalent iodine reagents have gained special attention as versatile and benign oxidants in several organic transformations. Moreover, in a multistep synthesis of natural bioactive heterocycles, organohypervalent iodine reagents are important source to achieve key intermediates for being safer alternatives to hazardous and metal-based reagents. This chapter summarizes the recent trends adapted by organic chemists mainly in the synthesis of biologically relevant five- and six-membered heterocycles using such diverse organohypervalent iodine reagents.