title: Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers.
abstract: Aiming to develop multitarget drugs for the anticancer treatment, a new class of chalcone-pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) conjugates linked through a 1,2,3-triazole moiety containing alkane spacers has been designed and synthesized. Combining these two core pharmacophore structures with modifications at A-C8/C-C2-position of PBD ring system yielded analogs with improved efficacy and have shown promising in vitro anticancer activity ranging from <0.1-2.92 μM. These PBD-conjugates caused G1 cell cycle arrest with effect on G1 cell cycle regulatory proteins such as Cyclin D1 and Cdk4. These conjugates also exhibited inhibitory effect on NF-kB, Bcl-XL proteins that play a vital role in breast cancer cell proliferation. These findings suggest that one of the compound 4d among this series is most effective and has potential for detailed investigations.
authors.affiliation: Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India. ahmedkamal@iict.res.in
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: S
authors.initials: S
authors.lastname: Prabhakar
authors.forename: M
authors.initials: M
authors.lastname: Janaki Ramaiah
authors.forename: P
authors.initials: P
authors.lastname: Venkat Reddy
authors.forename: Ch
authors.initials: Ch
authors.lastname: Ratna Reddy
authors.forename: A
authors.initials: A
authors.lastname: Mallareddy
authors.forename: Nagula
authors.initials: N
authors.lastname: Shankaraiah
authors.forename: T
authors.initials: T
authors.lastname: Lakshmi Narayan Reddy
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpavalli
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001569:Benzodiazepines / Q000737:chemistry*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D047188:Chalcones; D016328:NF-kappa B; D011758:Pyrroles; D014230:Triazoles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines