title: Rational modification of the lead molecule: Enhancement in the anticancer and dihydrofolate reductase inhibitory activity.
abstract: 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.
authors.affiliation: Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
authors.forename: Jagroop
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
authors.forename: Sukhmeet
authors.initials: S
authors.lastname: Kaur
authors.affiliation: Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India. Electronic address: palwinder_singh_2000@yahoo.com.
authors.forename: Palwinder
authors.initials: P
authors.lastname: Singh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase
keywords: Anti-cancer activity; Dihydrofolate reductase; Indole