Synthesis of imidazothiazole-chalcone derivatives as anticancer and apoptosis inducing agents.
A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. Interestingly, these chalcone derivatives induced G(0)/G(1)-phase cell-cycle arrest, down-regulation of G(1)-phase cell-cycle regulatory proteins such as cyclin D1 and cyclin E1, and up-regulation of CDK4. Moreover, these compounds elicit the characteristic features of apoptosis such as enhancement in the levels of p53, p21, and p27, suppression of NF-κB, and up-regulation of caspase-9. One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies.
Kamal
Ahmed
A
Chemical Biology Laboratory, Indian Institute of Chemical Technology, Hyderabad 500607, India. ahmedkamal@iict.res.in
Dastagiri
D
D
Ramaiah
M Janaki
MJ
Reddy
J Surendranadha
JS
Bharathi
E Vijaya
EV
Srinivas
Chatla
C
Pushpavalli
S N C V L
SN
Pal
Dhananjaya
D
Pal-Bhadra
Manika
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002599:Chalcone / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D016213:Cyclins; D007093:Imidazoles; D016328:NF-kappa B; D013844:Thiazoles; D002599:Chalcone; D018844:Cyclin-Dependent Kinases; D053453:Caspase 9