Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors.

A series of imidazopyridinyl-1,3,4-oxadiazole conjugates were synthesized and investigated for their cytotoxic activity and some compounds showed promising cytotoxic activity. Compound 8q (NSC: 763639) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10µM) on all human cancer cell lines. This compound was further evaluated at five dose levels (0.01, 0.1, 1, 10 and 100µM) to obtain GI50 values ranging from 1.30 to 5.64µM. Flow cytometric analysis revealed that compound 8q arrests the A549 cells in sub G1 phase followed by induction of apoptosis which was further confirmed by Annexin-V-FITC, Hoechst nuclear staining, caspase 3 activation, measurement of mitochondrial membrane potential and ROS generation. Topo II mediated DNA relaxation assay results showed that conjugate 8q could significantly inhibit the activity of topo II. Moreover, molecular docking studies also indicated binding to the topoisomerase enzyme (PDBID 1ZXN).

Sulfamic acid promoted one-pot three-component synthesis and cytotoxic evaluation of spirooxindoles.

A simple, mild and efficient method for the synthesis of pyrazolopyridine based spirooxindoles by the three-component reaction has been developed using sulfamic acid (H2NSO3H) as a green catalyst. The method involves use of water as a solvent which makes it eco-friendly. The catalyst used is readily available and is prominent for short reaction time, operational simplicity and high yields. After completion of the reaction the catalyst could be recovered and reused for up to four cycles without loss in catalytic activity. Employing this method a library of 34 compounds has been synthesized and investigated for their cytotoxicity against a panel of three human cancer cell lines. Some of the compounds like 4o and 4p exhibited remarkable cytotoxicities with IC50 values of 0.35µM and 1.92µM against MDA-MB-231 cell line.

Synthesis and anticancer potential of benzothiazole linked phenylpyridopyrimidinones and their diones as mitochondrial apoptotic inducers.

A series of benzothiazole linked phenylpyridopyrimidinones (8a-g) and their diones (9a-g) have been designed, synthesized and evaluated for their anticancer activity. Among the series one of the conjugate 8b showed significant cytotoxicity against human cervical cancer cell line ME-180 with IC50 value of 4.01µM. This compound was tested on the cell cycle perturbations and DNA damage. Flow cytometry analysis revealed that the compound 8b showed drastic cell cycle perturbations due to concentration dependent increase in the sub-G0 phase in ME-180 cell line. DNA fragmentation and Hoechst staining reveals that this compound induced cell death by apoptosis. Further caspase-3 and loss of mitochondrial membrane potential suggested that the compound induces cell death by apoptosis.

A domino Knoevenagel hetero-Diels-Alder reaction for the synthesis of polycyclic chromene derivatives and evaluation of their cytotoxicity.

A novel octahydrochromeno[4,3-a]xanthen-1(2H)-one derivatives has been prepared using 10mol% dl-proline in ethanol via a domino Knoevenagel hetero-Diels-Alder reaction of alkene-tethered chromene-3-carboxaldehyde with cyclic 1,3-diketones. This is not only the first example on the preparation of highly diastereoselective pentacyclic chromene derivatives from alkene appended chromene-3-carboxaldehyde in one-pot process at ambient temperature but also preliminary evaluation of the cytotoxic activity of these chromene derivatives. Some of these compounds are found to exhibit potent cytotoxicity against two carcinoma cell lines A549 and B-16.