title: Synthesis, DNA binding affinity and anticancer activity of novel 4H-benzo[g][1,2,3]triazolo[5,1-c][1,4]oxazocines.
abstract: A new class of tricyclic heterocycles 4H-benzo[g][1,2,3]triazolo[5,1-c][1,4]oxazocines was synthesized through a Knoevenagel condensation/azide-alkyne cycloaddition reaction cascade in one-pot operation. These eight membered ring containing heterocycles exhibited moderately high anticancer activity against four cancer cell lines; human cervix cancer cell line (HeLa), human prostate cancer cell line (DU145), human breast cancer cell line (MCF-7) and human breast adenocarcinoma epithelial cell line (MDA-MB-231). Our results indicate that these compounds have a weak cytotoxic effect on normal human mammary epithelial cell line (MCF-10A). Cell cycle and apoptosis assay indicate that they inhibit the cell cycle at the G2/M phase and induce apoptosis. Through the RED100assay, it is evident that they have potential to inhibit pBR 322 plasmid DNA cleavage by BamH1. UV-visible, fluorescence titration and viscosity studies suggested that these compounds possess DNA binding affinity.
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India and Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad-500037, India.
authors.forename: K N Visweswara
authors.initials: KN
authors.lastname: Sastry
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India and Department of Biotechnology, Acharya Nagarjuna University, Guntur-522510, India.
authors.forename: Sunitha Rani
authors.initials: SR
authors.lastname: Routhu
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India and Department of Biotechnology, Acharya Nagarjuna University, Guntur-522510, India.
authors.forename: Soma Gupta
authors.initials: SG
authors.lastname: Datta
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Hyderabad-500007, India.
authors.forename: Narayana
authors.initials: N
authors.lastname: Nagesh
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad-500037, India.
authors.forename: Bathini Nagendra
authors.initials: BN
authors.lastname: Babu
authors.affiliation: Centre for X-Ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.
authors.forename: Jagadeesh Babu
authors.initials: JB
authors.lastname: Nanubolu
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.
authors.forename: C Ganesh
authors.initials: CG
authors.lastname: Kumar
authors.affiliation: Applied Organic Chemistry Group, Chemical Science & Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam-785006, India. ram.cdri@gmail.com ahmedkamal@iict.res.in nagesh@ccmb.res.in.
authors.forename: Ram Awatar
authors.initials: RA
authors.lastname: Maurya
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India and Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Hyderabad-500037, India.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D010079:Oxazocines / Q000737:chemistry* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D010079:Oxazocines; D004247:DNA