title: Regioselective synthesis of polycyclic aza-oxa and aza-oxa-thia heteroarenes as Colo-205 and HepG2 carcinoma cells growth inhibitors.
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 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.
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Aromatic Plants, Kukrail Road, Lucknow 226015, India. Electronic address: hardesh11@yahoo.co.in.
authors.forename: Hardesh K
authors.initials: HK
authors.lastname: Maurya
authors.affiliation: Department of Chemistry, Lucknow University, Lucknow, UP 226007, India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Gautam
authors.affiliation: Department of Chemistry, University of Delhi, North Campus, Delhi 110007, India.
authors.forename: Ramendra
authors.initials: R
authors.lastname: Pratap
authors.affiliation: Department of Chemistry, Lucknow University, Lucknow, UP 226007, India. Electronic address: vishnutandon@yahoo.co.in.
authors.forename: Vishnu K
authors.initials: VK
authors.lastname: Tandon
authors.affiliation: Department of Chemistry, Lucknow University, Lucknow, UP 226007, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Division of SAIF, Central Drug Research Institute, Lucknow 226001, India.
authors.forename: Brijesh
authors.initials: B
authors.lastname: Kumar
authors.affiliation: Food, Drug and Chemical Toxicology Group, Indian Institute of Toxicology Research, Lucknow 226001, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Food, Drug and Chemical Toxicology Group, Indian Institute of Toxicology Research, Lucknow 226001, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Food, Drug and Chemical Toxicology Group, Indian Institute of Toxicology Research, Lucknow 226001, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Rajwanshi
authors.affiliation: Food, Drug and Chemical Toxicology Group, Indian Institute of Toxicology Research, Lucknow 226001, India. Electronic address: mditrc@rediffmail.com.
authors.forename: Mukul
authors.initials: M
authors.lastname: Das
authors.affiliation: Department of Chemistry, Lucknow University, Lucknow, UP 226007, India. Electronic address: vjiram@yahoo.com.
authors.forename: Vishnu Ji
authors.initials: VJ
authors.lastname: Ram
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells; D056945:Hep G2 Cells; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000166:cytology; D008113:Liver Neoplasms / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001372:Aza Compounds; D006571:Heterocyclic Compounds; D011083:Polycyclic Compounds; D013438:Sulfhydryl Compounds
keywords: Anti-cancer; Apoptosis; Benzo[b]oxepine; Benzo[b]thiepine; Diheteroaryl[c,e][1,2]diazepine; Inhibitors; Thiochromene