Abstract:
:Novel oxindole derivatives bearing substituted cyclopropane ring have been designed on the basis of docking studies with HIV-1 RT using the software DS 2.5 and synthesized as probable NNRTIs against HIV-1 using rhodium(II) acetate-catalyzed stereoselective cyclopropanation reaction. The cyclopropane isomer, having trans relationship with respect to carbonyl of lactam moiety and functional group on the cyclopropane ring, was the major product in all cases along with a small amount of cis and methylene products. The trans isomers interacted well with HIV-1 RT through H-bonding with amino acids, like Lys101, Lys103, His235, Tyr318, constituting the non-nucleoside inhibitor binding pocket (NNIBP) during docking experiments. However, the compounds showed very little activity when subjected to in vitro anti-HIV-1 screening using β-galactosidase assay (TZM-bl cells) and GFP quantification (CEM-GFP cells). The very low level of in vitro HIV inhibition, in comparison to predicted EC(50) values on the basis of computational studies, during CEM-GFP screening using AZT as positive control indicated that probably the HIV RT is not the viral target and the molecules work through some different mechanism.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Kumari G,Nutan,Modi M,Gupta SK,Singh RKdoi
10.1016/j.ejmech.2011.01.037subject
Has Abstractpub_date
2011-04-01 00:00:00pages
1181-8issue
4eissn
0223-5234issn
1768-3254pii
S0223-5234(11)00059-6journal_volume
46pub_type
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