Regioselective synthesis of polycyclic aza-oxa and aza-oxa-thia heteroarenes as Colo-205 and HepG2 carcinoma cells growth inhibitors

European Journal of Medicinal Chemistry,Volume 81, 23 June 2014, Pages 367–377 Available online 5 May 2014
Hardesh K. Maurya, Sanjay K. Gautam, Ramendra Pratap, Vishnu K. Tandon, Abhinav Kumar, Brijesh Kumar, Shruti Saxena, Deepti Tripathi, Meenakshi Rajwanshi, Mukul Das, Vishnu Ji Ram

DOI: http://dx.doi.org/10.1016/j.ejmech.2014.05.013

Abstract

An efficient regioselective synthesis of polycyclic diheteroaryl[b,d]pyrans and diheteroaryl[c,e][1,2]diazepines has been reported through ring transformation reactions of 2-oxo-2,5-dihydrothiochromeno[4,3-b]pyrans (3,4), 2-oxo-5,6-dihydro-2H-benzo[b]pyrano[2,3-d]oxepine/thiepine (8, 9) and 6-oxo-3,6-dihydro-2H-naphtho[1,2-b]pyrano[2,3-d]oxepine (15) by hydrazine, at ambient and reflux temperature. Nine compounds viz 5a,b; 10a,c,d; 12b; 13b; 16 and 1-methylthio-5,6-dihydrobenzo[f]quinoline (0.1-100 μM) were screened for their cytotoxicity in normal (IEC-6), carcinoma (Colo-205) and Hep G2 cell lines. None of the compounds showed cytotoxicity in normal IEC-6 cells while 10a,d and 16 resulted in killing of Colo-205 cells with IC₅₀ ranging between 20-60μM while 10c and 13b caused killing of HepG2 cells with IC₅₀ values ranging between 60-80 μM concentration. Further, 10a,d and 16 caused apoptosis through a cascade of mitochondrial pathway in Colo-205 cells indicating anticancerous potential against intestinal cancer. Interestingly, compounds 10c and 13b exhibited apoptosis through mitochondrial pathway in HepG2 cells suggesting anticancer activity against hepatic cancer.