Design and synthesis of new 2,5-disubstituted-1,3,4-oxadiazole analogues as anticancer agents

Abstract

In continuance of our search for new anticancer agents, we report herein the design, synthesis, and anticancer evaluation of oxadiazole analogues. Two series (4a-h and 4i-q) of new oxadiazole analogues were designed based on heterocyclic (1,3,4-oxadiazole)-linked aryl core of IMC-038525 (tubulin polymerization inhibitor), NSC 776715, and NSC 776715 and synthesized. All the compounds were fully characterized by infrared, nuclear magnetic resonance spectroscopy, and mass spectral data and the purity of compounds was checked by elemental analysis (C, H, and N analysis). Further seven compounds were evaluated for anticancer activity on nine different panels of 60 cell lines (60 NCI cancer cell lines) according to the National Cancer Institute screening protocol and percent growth and percent growth inhibition was calculated at 10 µM drug concentration. Ten compounds were evaluated for anticancer activity on two cancer cell lines (HeLa and MDA-MB-435) as per the standard protocol reported at four different drug concentrations (10−7, 10−6, 10−5, and 10−4 µM) and GI50, LC50, and TGI dose-related parameters were calculated. The compound 4j showed maximum anticancer activity at 10 µM, and was found to have higher sensitivity against MOLT-4, IGROV1, HCT-116, and K-562 with percent growth inhibitions of 50.38, 48.45, 46.26, and 46.26 respectively. The compound 4j showed superior anticancer activity than imatinib on 41 human cancer cell lines. The compound 4p showed anticancer activity with GI50 of 36.7 and 46.5 µM against HeLa and MDA-MB-435 cell lines, respectively.