Rational modification of the lead molecule: Enhancement in the anticancer and dihydrofolate reductase inhibitory activity.
By using molecular docking studies, the practice of fragment based drug discovery is conceptualized by introducing oxindole and iso-propanol moieties in our previous lead molecule 1. The resulting compound 2 exhibited competitive inhibition and favorable Ka and Ki for hDHFR. The screening of compound 2 at 60 cell line panel of human tumor cell lines showed its considerably better efficacy than compound 1 and hence put the candidature of 2 on stronghold for further studies.
['Kaur|Jagroop|J|', 'Kaur|Sukhmeet|S|', 'Singh|Palwinder|P|']
D000970:Antineoplastic Agents D045744:Cell Line, Tumor D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D005493:Folic Acid Antagonists D006801:Humans D062105:Molecular Docking Simulation D015394:Molecular Structure D013329:Structure-Activity Relationship D013762:Tetrahydrofolate Dehydrogenase
Dihydrofolate reductase Anti-cancer activity Indole