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.

Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents

Bioorganic & Medicinal Chemistry Letters, Volume 24, Issue 13, 1 July 2014, Pages 2892–2896, Available online 4 May 2014
Vinay Pathak, Hardesh K. Maurya, Sandeep Sharma, Kishore K  Srivastava, Atul Gupta

DOI: http://dx.doi.org/10.1016/j.bmcl.2014.04.094

Abstract

Various substituted 4,6-diarylpyrimidin-2-amine (4), 4,6-diaryl-2-(heteroaryl)pyrimidine (6) and 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-1-yl)ethanone (7) derivatives were synthesized in good yields using simple methodology. The synthesized compounds (4-7) were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. Compounds 4a, 6b, 7b, and 7c exhibited significant anti-tubercular activity at MIC values 25, 25, 12.5 and 12.5 μM concentration. In vitro cytotoxicity data using non cancerous hepatic monocytes (THP-1) cells indicated that most active compounds 7b and 7c were safe as their MIC values were much lower than their cytotoxic values