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Quinazolinone and benzimidazole represent as important and abundant classes of fused nitrogen-containing heterocycle. A series of two isomeric quinazolinone-benzimidazole conjugates is synthesized and substitutes with different aromatic rings. These compounds are well characterized by 1 H and 13 C NMR as well as mass spectrometry. Compounds are then evaluated by dihydrofolate reductase inhibitory activity. In vitro assay shows that some compounds are exhibiting significant dihydrofolate reductase inhibitory activities. Compound 14 shows comparable or even superior inhibitory activity with IC 50 value of 0.011 μM in contrast to methotrexate (IC 50 = 0.02 μM). The preliminary interactive investigation of compound 14 is studied with calf thymus DNA by UV–visible and fluorescence spectroscopy. It reveals that compound 14 is effectively intercalated with ct-DNA to form 14 .DNA complex which is further supported by ethidium bromide (EB) displacement studies. The compound 14 also shows strong interaction with bovine serum albumin that can helpful in the design, modification and screening of drug molecules. The binding interactions of compound 14 with bovine serum albumin demonstrate that hydrogen bonds and van der Waals forces play important roles in the strong association of compound 14 .BSA. These compounds can be considered as useful templates for future development and further derivatization or modification will be helpful to obtain more potent compounds. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel regioisomeric hybrids of quinazoline/benzimidazole viz. (3-allyl-2-methyl-3H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine and (1-allyl-2-methyl-1H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine of biological interest were synthesized. All the synthesized compounds were well characterized by 1H and 13C NMR as well as mass spectroscopy. The newly synthesized compounds were screened for in vitro antitumor activities against 60 tumor cell lines panel assay. A significant inhibition for cancer cells were observed with compound 9 and also more active against known drug 5-fluorouracil (5-FU) in some tumor cell lines. Compound 9 displayed appreciable anticancer activity against leukemia, colon, melanoma, renal and breast cancer cell lines. [Copyright &y& Elsevier]

Abstract: By combining the structural features of quinazoline and benzimidazole, new hybrid regioisomeric molecules with substituted primary amines have been synthesized. Evaluation of these molecules over 60 cancer cell line panel has identified three molecules as most potent anticancer agents. Compound 10 showed ten and eleven folds more activity than respective quinazoline and benzimidazole class of compounds with GI50 value of 1.64μM. Compound 11 (GI50 value of 0.81μM) showed almost twenty and twenty-two fold more activity than quinazoline and benzimidazole analogue, respectively while compound 12 (GI50 value of 4.52μM) has four fold more activity than quinazoline and benzimidazole analogue. In vitro evaluation of compound 11 exhibited remarkable anticancer activity towards colon cancer cell lines and prostate cancer cell lines at five dose concentrations with GI50 values of 0.34 and 0.31μM, respectively. [Copyright &y& Elsevier]