title: Design and synthesis of C3-tethered 1,2,3-triazolo-β-carboline derivatives: Anticancer activity, DNA-binding ability, viscosity and molecular modeling studies.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar.niperhyd@gov.in.
authors.forename: Nagula
authors.initials: N
authors.lastname: Shankaraiah
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Jadala
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Nekkanti
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Kishna Ram
authors.initials: KR
authors.lastname: Senwar
authors.affiliation: CSIR-Centre for Cellular & Molecular Biology, Hyderabad 500 607, India. Electronic address: nagesh@ccmb.res.in.
authors.forename: Narayana
authors.initials: N
authors.lastname: Nagesh
authors.affiliation: Pharmacology and Toxicology Department, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Shrivastava
authors.affiliation: Pharmacology and Toxicology Department, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: V G M
authors.initials: VG
authors.lastname: Naidu
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
authors.forename: Manda
authors.initials: M
authors.lastname: Sathish
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014783:Viscosity
chemical_list: C000613600:2-((1-((1-(3,4-dimethoxyphenyl)-9H-pyrido(3,4-b)indol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo(de)isoquinoline-1,3(2H)-dione; C000613599:5-methyl-2-((1-((1-(3,4,5-trimethoxyphenyl)-9H-pyrido(3,4-b)indol-3-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)isoindoline-1,3-dione; D000970:Antineoplastic Agents; D002243:Carbolines; D014230:Triazoles; D004247:DNA
keywords: 1,2,3-Triazoles; Click reaction; Cytotoxicity; DNA-binding ability; Minor groove binder; Molecular modeling; β-Carbolines