Novel 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues as cytotoxic agents.
A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21 and 28 exhibited good pharmacokinetic properties. These compounds were further evaluated for their in vivo efficacy in modified hollow fibre assay (HFA).
Sharma
Vedula M
VM
Discovery Chemistry, Dr. Reddy's Laboratories, Discovery Research, Miyapur, Hyderabad, 500 050, India. sarmavm@drreddys.com
Adi Seshu
K V
KV
Vamsee Krishna
C
C
Prasanna
P
P
Chandra Sekhar
V
V
Venkateswarlu
A
A
Rajagopal
Sriram
S
Ajaykumar
R
R
Deevi
Dhanvanthri S
DS
Rao Mamidi
N V S
NV
Rajagopalan
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007212:Indolizines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D010599:Pharmacokinetics; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007212:Indolizines