title: Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies.
abstract: A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10 μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50values of 1.30 μM, 1.43 μM, 2.38 μM and 2.18 μM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala, 147004, India.
authors.forename: Prinka
authors.initials: P
authors.lastname: Singla
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala, 147004, India. Electronic address: vluxami@thapar.edu.
authors.forename: Vijay
authors.initials: V
authors.lastname: Luxami
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110 067, India.
authors.forename: Raja
authors.initials: R
authors.lastname: Singh
authors.affiliation: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110 067, India.
authors.forename: Vibha
authors.initials: V
authors.lastname: Tandon
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala, 147004, India. Electronic address: kpaul@thapar.edu.
authors.forename: Kamaldeep
authors.initials: K
authors.lastname: Paul
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D007364:Intercalating Agents; D011743:Pyrimidines; D059003:Topoisomerase Inhibitors; D012710:Serum Albumin, Bovine; D004247:DNA; D004250:DNA Topoisomerases, Type II
keywords: Antitumor activity; Benzimidazole; Bovine serum albumin; Pyrazolo[3,4-d]pyrimidine; ct-DNA