Elucidation of anti-proliferative and anti-angiogenic potential ofnovel imidazo[2,1-b][1,3,4]thiadiazole derivatives in Ehrlich ascites tumor model

Abstract

Introduction and Aim:Synthesis of antineoplastic drugs is challenging and shrouded with possibilities of multidrug resistance and numerous side effects. Imidazo[2,1-b][1,3,4]thiadiazole moieties exhibit tremendous scope as novel anti-cancer molecules. In the present study, we synthesize and characterize a series of 5(a-e) Imidazo[2,l-b][1, 3,4]thiadiazole derivatives andevaluate them for antiproliferative properties using in vivo, in vitro , andin silicoapproach. Materials and Methods:The in vivostudies conducted using murine Ehrlich Ascites Cancer (EAC) cell model establishes that treatment with 5c reduces the tumorigenesisby promoting apoptosis inEAC-bearing mice. The cells retrieved from the control andtreatment arms of EAC cell bearing mice were used for nuclear and Giemsa staining, DNA fragmentation, RT-PCR and chorioallantoic membrane evaluations. Results:5cinduces apoptosis, plasma membrane degradation, up-regulation of apoptotic genes and anti-angiogenic characteristics. In vitro evaluation of 5cusing,various cancer cell linesagainst normal fibroblast 3T3 L1 cells confirm 5c sensitivity to MCF-7 with IC50value of 8?M. 5c exudes marked reduction in cell viability, dual nuclear staining,and long-term colony formationassays in thesecells. Conclusion:5c inhibits the growth and proliferation of cancer cells. The results of our molecular docking predictions further substantiate our claim. This study is valuable as 5c exhibitsapromising approach for the treatment of cancer and itsanti-proliferative potential can be exploited for designing novel anticancer drugs in the near future. Keywords:Imidazo[2,1-b][1,3,4]thiadiazole derivatives;NMRcytotoxicity, EAC cell;apoptosis;anti-angiogenesis.