Maurya Hardesh K, Gautam Sanjay K, Pratap Ramendra, Tandon Vishnu K, Kumar Abhinav, Kumar Brijesh, Saxena Shruti, Tripathi Deepti, Rajwanshi Meenakshi, Das Mukul, Ram Vishnu Ji
Medicinal Chemistry Department, CSIR-Central Institute of Aromatic Plants, Kukrail Road, Lucknow 226015, India.
Department of Chemistry, Lucknow University, Lucknow, UP 226007, India.
Eur J Med Chem. 2014 Jun 23;81:367-77. doi: 10.1016/j.ejmech.2014.05.013. Epub 2014 May 5.
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 HepG2 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 20-60 μM while 10c and 13b caused killing of HepG2 cells with IC50 values ranging 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.
据报道，通过2-氧代-2,5-二氢硫代色烯并[4,3-b]吡喃（3,4）、2-氧代-5,6-二氢-2H-苯并[b]吡喃并[2,3-d]氧杂环庚三烯/硫杂环庚三烯（8,9）和6-氧代-3,6-二氢-2H-萘并[1,2-b]吡喃并[2,3-d]氧杂环庚三烯（15）在室温和回流温度下与肼发生的环转化反应，实现了多环二杂芳基[b,d]吡喃和二杂芳基[c,e][1,2]二氮杂卓的高效区域选择性合成。筛选了9种化合物，即5a,b；10a,c,d；12b；13b；16和1-甲硫基-5,6-二氢苯并[f]喹啉（0.1 - 100 μM）在正常（IEC-6）、癌（Colo-205）和HepG2细胞系中的细胞毒性。这些化合物在正常IEC-6细胞中均未显示细胞毒性，而10a,d和16导致Colo-205细胞死亡，IC50范围为20 - 60 μM，而10c和13b导致HepG2细胞死亡，IC50值在60 - 80 μM浓度范围内。此外，10a,d和16通过Colo-205细胞中的线粒体途径级联引发凋亡，表明对肠癌具有抗癌潜力。有趣的是，化合物10c和13b在HepG2细胞中通过线粒体途径表现出凋亡，提示对肝癌具有抗癌活性。
