Original article Microwave assisted synthesis of dihydrobenzo[4,5]imidazo[1,2-a] pyrimidin-4-ones; synthesis, in vitro antimicrobial and anticancer activities of novel coumarin substituted dihydrobenzo[4,5]imidazo [1,2-a]pyrimidin-4-ones Kallimeledoddi B. Puttaraju a , Kalegowda Shivashankar a, * , Chandra b , M. Mahendra b , Vijaykumar P. Rasal c , Ponnuru N. Venkata Vivek c , Khushboo Rai c , Maibam Beebina Chanu c a P.G. Department of Chemistry, Central College Campus, Bangalore University, Bangalore 560 001, Karnataka, India b Department of Studies in Physics, Manasagangothri, University of Mysore, Mysore 570 006, Karnataka, India c Department of Pharmacology, KLE University College of Pharmacy, Belgaum 590 010, Karnataka, India article info Article history: Received 19 February 2013 Received in revised form 17 July 2013 Accepted 22 July 2013 Available online 15 August 2013 Keywords: 4-Bromomethylcoumarins Coumarins Benzimidazole Pyrimidine abstract The present article describes the synthesis of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (2aeh) under microwave irradiation. The product was obtained in excellent yield (74e94%) in a shorter reaction time (2 min). These molecules (2a, b) further reacted with various substituted 4-bromomethylcoumarins (3aef) to yield a new series of coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones (4aeh). The structure of all the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against three Gram-positive bacteria viz., Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and three Gram-negative bacteria viz., Escherichia coli, Kleb- siella pneumonia, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Fusarium oxysporum, Penicillium chrysogenum and anti- cancer activity against Dalton’s Ascitic Lymphoma (DAL) cell line. In general, all the compounds possessed better antifungal properties than antibacterial properties. The coumarin substituted dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one (4g) (R ¼ i-Pr, R 1 ¼ 6-Cl) was found to be the most potent cytotoxic compound (88%) against Dalton’s Ascitic Lymphoma cell line at the concentration of 100 mg/mL. Ó 2013 Elsevier Masson SAS. All rights reserved. 1. Introduction Dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-one is a class of fused tricyclic system having three nitrogen atoms. The design concept of dihydrobenzo[4,5]imidazo[1,2-a]pyrimidin-4-ones has arised from the broad spectrum and the wide range of biological activities of the benzimidazole and pyrimidine. Benzimidazole derivatives [1] exhibited high cytotoxicity against HepG-2 cells and good EGFR inhibitory activity. 2- Substituted-5-amino-benzimidazoles [2] possessed significant cytotoxicity against breast cancer cell line MCF-7. 1,2,5- Trisubstituted benzimidazoles [3] and benzimidazolo pyrimidine conjugates [4] were found to be antitumor agents against Melanoma cell lines. QSAR analyses of 2-aminobenzimidazole de- rivatives [5] were studied on the relation between acute toxicity and the octanol/water partition coefficient. 6-Butylfuro[2,3-d]pyrimidine derivatives [6] showed the high- est cytostatic activity against Malignant leukemia and T-lympho- cyte cells. 5-Benzylidine barbiturate derivatives [7] inhibited the growth of mushroom tyrosinase and Gram-positive bacteria Staphylococcus aureus. Pyrimidine bases [8] exerted pronounced antiproliferative activity against the HeLa and MiaPaCa-2 cell lines. 1-Adamantyl thiopyrimidines [9] displayed the significant cyto- toxic activity particularly against H69AR cell line. Pyrimidine ana- logs of indane-1,3-diones [10] showed significant reduction in ulcerogenic activity when compared to standard drug Indomethacin. The fusion of benzimidazole and pyrimidine pharmacophores in a single molecular frame work and the study of subsequent influ- ence on the biological activities are of current interest. * Corresponding author. Tel.: þ91 80 22961249. E-mail address: shivashankark@gmail.com (K. Shivashankar). Contents lists available at ScienceDirect European Journal of Medicinal Chemistry journal homepage: http://www.elsevier.com/locate/ejmech 0223-5234/$ e see front matter Ó 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.ejmech.2013.07.015 European Journal of Medicinal Chemistry 69 (2013) 316e322