Design and synthesis of C3-tethered 1,2,3-triazolo-β-carboline derivatives: Anticancer activity, DNA-binding ability, viscosity and molecular modeling studies

• Published in: Bioorganic chemistry Vol. 64; pp. 42 - 50
• Main Authors: Shankaraiah, Nagula, Jadala, Chetna, Nekkanti, Shalini, Senwar, Kishna Ram, Nagesh, Narayana, Shrivastava, Shweta, Naidu, V.G.M., Sathish, Manda, Kamal, Ahmed
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.02.2016; Elsevier
• Subjects: 1,2,3-Triazoles; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biochemistry & Molecular Biology; Carbolines - chemical synthesis; Carbolines - chemistry; Carbolines - pharmacology; Cell Line, Tumor; Chemistry; Chemistry, Organic; Circular Dichroism; Click reaction; Cytotoxicity; DNA - chemistry; DNA-binding ability; Humans; Life Sciences & Biomedicine; Minor groove binder; Molecular Docking Simulation; Molecular modeling; Physical Sciences; Science & Technology; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - pharmacology; Viscosity; β-Carbolines; 1,2,3-Triazoles; Minor groove binder; DNA-binding ability; Molecular modeling; Cytotoxicity; Click reaction; β-Carbolines; APOPTOSIS; beta-Carbolines; PORPHYRINS; POTENT; AFFINITY; CLICK-CHEMISTRY; AGENTS
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2015.11.005

A series of new DNA-interactive C3-tethered 1,2,3-triazolo-β-carboline derivatives have been synthesized via ‘click’ reaction and evaluated for their in vitro cytotoxicity as well as DNA binding affinity. [Display omitted] •A series of C3-tethered 1,2,3-triazolo-β-carboline derivatives were synthesized.•Cytotoxicity tested on HeLa, HT-29, MCF, PC-3 and HGC-27 cell lines.•DNA-binding affinity was evaluated by spectroscopic studies.•Compounds showed potent DNA electrostatic binding and in vitro cytotoxicity.•Viscometric titration and molecular docking established DNA minor groove binding. A series of new DNA-interactive C3-tethered 1,2,3-triazolo-β-carboline derivatives have been synthesized via ‘click’ reaction and evaluated for their in vitro cytotoxicity as well as DNA binding affinity. Interestingly, these hybrids have displayed potent in vitro cytotoxicity in comparison to Harmine against the HT-29 (colon cancer) and HGC-27 (gastric cancer) cell lines. The compounds 7f, 7k, 7n and 7s appear to be more effective against the HGC-27 cell line, among which compound 7f showed the highest cytotoxicity (5.44±0.58, IC50 μM). The compounds 7e and 7f appear to be more active against the HT-29 cell line, among which compound 7f exhibited the highest cytotoxicity (3.67±0.62, IC50 μM). To gain more insight into the DNA-binding ability, spectroscopic techniques such as UV–Visible, fluorescence and circular dichroism studies were performed. Viscosity measurements and molecular docking studies substantiate that these compounds indeed bind to DNA via the minor groove.