title: Synthesis and biological evaluation of novel Mannich bases of 2-arylimidazo[2,1-b]benzothiazoles as potential anti-cancer agents.
abstract: A new series of Mannich bases of 2-arylimidazo[2,1-b]benzothiazoles were synthesized and evaluated for their anti-cancer activity. These compounds showed better cytotoxicity activity with IC(50) values ranging from 2.8 to 8.0 μM in HepG2, MCF-7 and HeLa cell lines. Further mechanism aspects responsible for the anti-cancer activity of two promising compounds 3c and 3f in HepG2 cell line were studied. Interestingly, 3c, 3f induced G2/M cell cycle arrest with down regulation of cyclin B and up regulation of Chk2 protein. Moreover, compounds 3c, 3f also showed the characteristic features of apoptosis such as enhancement in the levels of caspase-3. Treatments with compounds led to a decrease in levels of vital cell proliferation proteins such as Jun (C-Jun, JunB), p38 MAPK, p-JNK and PKCα. The compound 3f of the series could be considered as the potential lead for its development as a novel anti-cancer agent.
authors.affiliation: Fluoroorganic Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. kumbhare@iict.res.in
authors.forename: Ravindra M
authors.initials: RM
authors.lastname: Kumbhare
authors.forename: K
authors.initials: K
authors.lastname: Vijay Kumar
authors.forename: M
authors.initials: M
authors.lastname: Janaki Ramaiah
authors.forename: Tulshiram
authors.initials: T
authors.lastname: Dadmal
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpavalli
authors.forename: Debasmita
authors.initials: D
authors.lastname: Mukhopadhyay
authors.forename: B
authors.initials: B
authors.lastname: Divya
authors.forename: T
authors.initials: T
authors.lastname: Anjana Devi
authors.forename: Umesh
authors.initials: U
authors.lastname: Kosurkar
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008352:Mannich Bases / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D008352:Mannich Bases; D013844:Thiazoles