title: DNA-binding affinity and anticancer activity of β-carboline-chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis.
abstract: A new series of DNA-interactive β-carboline-chalcone conjugates have been synthesized and evaluated for their in vitro cytotoxicity and DNA-binding affinity. It has been observed that most of these new hybrids have shown potent cytotoxic activities on A-549 (lung adenocarcinoma) cell lines with IC50 values lower than 10 μM. The hybrid 7b is more effective against some of the selected cancer cell lines with IC50 values less than 50 μM. In addition, compounds 7e, 7k, 7p-u has displayed significant elevation in ΔTm of DNA in comparison to Adriamycin, suggesting significant interaction and remarkable DNA stabilization. The DNA intercalation of these new hybrids has been investigated by fluorescence titration, DNA viscosity measurements, molecular docking as well as molecular dynamics and the results are in agreement with the thermal denaturation studies.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.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: K P
authors.initials: KP
authors.lastname: Siraj
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: Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Vunnam
authors.initials: V
authors.lastname: Srinivasulu
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
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: Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Manda
authors.initials: M
authors.lastname: Sathish
authors.affiliation: Pharmacology Department, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: M V P S
authors.initials: MV
authors.lastname: Vishnuvardhan
authors.affiliation: Pharmacology Department, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Sistla
authors.initials: S
authors.lastname: Ramakrishna
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India; Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Jadala
authors.affiliation: CSIR-Centre for Cellular & Molecular Biology, Hyderabad 500 607, India.
authors.forename: Narayana
authors.initials: N
authors.lastname: Nagesh
authors.affiliation: Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India. Electronic address: ahmedkamal@iict.res.in.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D007364:Intercalating Agents; D002599:Chalcone; D004247:DNA
keywords: Anticancer activity; Chalcone; Claisen–Schmidt condensation; DNA-binding ability; Molecular modelling; β-Carboline