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Abstract
Design, synthesis and evaluation of Novel 1-(Substituted Acetyl)-4-(10-Bromo-8-Chloro-5,6-Dihydro-11H-Benzo[5,6]Cyclohepta[1,2-B]Pyridine-11-Ylidene)piperidines as antitumor agents and farnesyl protein transferase inhibitors
Author(s): PS Gatne1, CL Viswanathan1, Premlata K Ambre1, Aarti Juvekar2
1Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai-400 098, India 2Anticancer Drug Screening Facility (ACDSF), Navi Mumbai-410 210, India
Correspondence Address:
P S Gatne Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai-400 098 India E-mail: parag507@gmail.com
1Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai-400 098, India 2Anticancer Drug Screening Facility (ACDSF), Navi Mumbai-410 210, India
Correspondence Address:
P S Gatne Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai-400 098 India E-mail: parag507@gmail.com
Eight novel 1-(substituted acetyl)-4-(10-bromo-8-chloro-5,6-dihydro-11H-benzo[5,6] cyclohepta [1,2-b] pyridine-11-ylidene)piperidines were designed by incorporating zinc binding groups to enhance activity. The designed molecules were synthesized and were evaluated for antitumor activity in vitro in five cell lines and for farnesyl protein transferase inhibition. Test compounds (6a-h) exhibited antitumor activity in most of the cell lines but were less potent than adriamycin. Compound 6e was most active with IC 50 values of <15 μM in two cell lines tested. Test compounds also exhibited potent FPT inhibitory activity and 6c was most potent with IC 50 value of <30 μM.
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