title: Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA.
abstract: A series of thirty two novel pyrrolo[2,3-b]pyridine analogues synthesized, characterized ((1)H NMR, (13)C NMR and MS) and cytotoxic evaluation of these molecules carried out over a panel of three human cancer cell lines including A549 (lung cancer), HeLa (cervical cancer) and MDA MB-231 (breast cancer), using sulforhodamine B assay method. Few molecules such as 5c, 5d, 5e, 5h, 5k, 5m, 5n, 5q, 5r, 7f, 7j, 7g and 7k exhibited maximum growth inhibitory action against the tested cancer cell lines at lower micro molar concentration. Noticeably, compounds exhibited good growth inhibition in all three cancer cell lines in the range of 0.12 μM-9.84 μM. Further study exposed that one of the active compound 5d could efficiently intercalate into calf thymus DNA to form 5d-DNA complex which might block DNA replication to influence their antiproliferative activity. The molecular interactions of all the synthesized analogs were also supported by molecular docking simulations. We believe that further optimization of these compounds will lead to potential anticancer agents.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, 500 078, Telangana, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: Narva
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, 500 078, Telangana, India.
authors.forename: Surendar
authors.initials: S
authors.lastname: Chitti
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, Telangana, India.
authors.forename: Bhaskara Rao
authors.initials: BR
authors.lastname: Bala
authors.affiliation: National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, 500037, Telangana, India.
authors.forename: Mallika
authors.initials: M
authors.lastname: Alvala
authors.affiliation: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500007, Telangana, India.
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, 500 078, Telangana, India. Electronic address: kvgc@hyderabad.bits-pilani.ac.in.
authors.forename: Venkata Gowri Chandra Sekhar
authors.initials: VG
authors.lastname: Kondapalli
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011725:Pyridines; D011758:Pyrroles; D004247:DNA; C427203:calf thymus DNA; C486292:pyrrolo(2, 3-b)pyridine
keywords: 1,2,3-Triazole; Antiproliferative activity; Calf thymus DNA; Pyrrolo[2,3-b]pyridine