title: Synthesis, in vitro antitumor activity, dihydrofolate reductase inhibition, DNA intercalation and structure-activity relationship studies of 1,3,5-triazine analogues.
abstract: A series of triazine-benzimidazoles with 4-fluoroaniline substitution has been designed and synthesized. These compounds were further substituted with different primary and secondary amines. The structures of newly synthesized compounds were confirmed by (1)H, (13)C NMR, mass spectrometry and, in case of compound 18, by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumor cell lines at one dose and five dose concentration levels. Compounds 7, 8 and 22 have been found to be the most active antitumor agents with GI50 values of 1.77, 1.94 and 2.87μM, respectively. The synthesized compounds were then evaluated for their inhibitory activity to mammalian dihydrofolate reductase. Compound 22 was depicted as the most active compound for the inhibition of dihydrofolate reductase with IC50 value of 2.0nM. DNA binding studies were also revealed strong interacting properties of triazine derivatives towards calf thymus-DNA.
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala 147001, India.
authors.forename: Prinka
authors.initials: P
authors.lastname: Singla
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala 147001, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Luxami
authors.affiliation: School of Chemistry and Biochemistry, Thapar University, Patiala 147001, India. Electronic address: kpaul@thapar.edu.
authors.forename: Kamaldeep
authors.initials: K
authors.lastname: Paul
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D005493:Folic Acid Antagonists; D007364:Intercalating Agents; C000613476:N-(3-benzyl-2-methyl-3H-benzimidazol-5-yl)-N'-(4-fluorophenyl)-N'-(2-morpholin-4-yl-ethyl)-(1,3,5)triazine-2,4,6-triamine; D014227:Triazines; D004247:DNA; C427203:calf thymus DNA
keywords: Anticancer; Benzimidzole; DNA interaction; Dihydrofolate reductase; Structure–activity relationship; Triazine