Send Orders for Reprints to reprints@benthamscience.ae Anti-Infective Agents, 2015, 13, 000-000 1 2211-3525/15 $58.00+.00 © 2015 Bentham Science Publishers Synthesis and Antiviral Activity of Dihydropyrimidines - Ciprofloxacin Mannich bases Against Various Viral Strains Rajasekhar R. Alavala 1 , Umasankar Kulandaivelu 1 , Pochaiah Bonagiri 1 , Shireesha Boyapati 2* , Venkatesan Jayaprakash 3 and Ananda T. Subramaniam 4 1 Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Hanamkonda 506001, India; 2 Department of Pharmaceutical Chemistry, Telangana University, Nizamabad, 503322, India; 3 Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi 835215, India; 4 Swamy Vivekanandha College of Pharmacy, Elayampalayam-637 205, Tiruchengode, Namakkal, Tamil Nadu, India Abstract: Dihydropyrimidinone is considered as a pharmacophoric skeleton in many drug discovery programmes. We have synthesized a wide range of dihydropyrimidinone analogues using microwave energy in the present investigation. Regioselectivity in these structures is achieved by the influence of weak base like potassium carbonate and synthesized some novel dihydropyrimidine N- and O-Mannich bases of ciprofloxacin (3a-j, 4a-g). All the synthesized molecules have been evaluated for their antiviral activ- ity against hepatitis C, hepatitis B, vaccinia, cowpox, severe acute respiratory syndrome, West Nile, dengue, Venezuelan equine encephalitis viruses, Flu A (H1N1, H3N2 and H5N1) and Flu B viral strains as well as for their cytotoxicity using standard protocols. An attempt was made to interpret the structure activity relation of compounds with their antiviral ac- tivity data. Compounds 3a, 3e, 3f, 4e, 4g were found to be active against Flu A (H1N1), TCRV, hepatitis B, yellow fever, vaccinia virus respectively. Out of O- and N-mannich bases, O-mannich bases were found to be more potent with high se- lectivity index. Keywords: Antiviral activity, dihydropyrimidinones, hepatitis B, influenza virus A (H1N1), microwave technology, regiose- lectivity, TCRV, vaccinia virus, yellow fever. INTRODUCTION Pyrimidinones or Dihydropyrimidinones (DHPMs) are well known for their wide range of bioactivities. They are present throughout nature in various forms and are the build- ing blocks of numerous natural compounds from antibiotics to vitamins, purines, co-enzymes, liposacharides and nucleo- side bases. Several modifications of this scaffold for drug discovery against diseases and its relative importance in na- ture make it an interesting heterocyclic ring of study. In the past decades, a wide range of biological effects including antitumor [1], antibacterial [2], antifungal [3], anti- inflammatory [4], antidiabetic [5] and analgesic activities have been ascribed to these partly reduced pyrimidine de- rivatives. In addition, these compounds have been proven as potential α 1a -adrenergic antagonists [6], vasodilators [7], antiatherosclerotic [8], antiplatelet aggregation [9] and neu- ropeptide antagonists [10]. Recently dihydropyrimidines have emerged as anticonvulsant [11], antitubercular [12], antimalarial [13], molluscicidal [14] and antiviral [15] in- cluding anti-HIV agents by acting on multiple targets. The scope of this pharmacophore has been further widening with *Address correspondence to this author at the Department of Pharmaceuti- cal Chemistry, Telangana University, Nizamabad-503322, India; Tel: 08461-222211 (Off), Mobile: 9848906357; Fax: 08461-222212; E-mail: sirimedchem@gmail.com the aryl substitution on ring at positions 4 th or 6 th or both can be considered as an important class of substances in organic and medicinal chemistry. On the other hand, Mannich bases also act as important pharmacophore or bioactive leads which are further used for synthesis of various potential agents of high medicinal value. These are physiologically reactive because of the basic func- tion rendering the molecule soluble in aqueous solvent when it is transformed into ammonium salt [16]. Mannich bases are known to possess potent activities like anti-inflammatory, analgesic, anticancer, antibacterial, antifungal, anticonvul- sant, anthelmintic, antitubercular, anti-HIV, antimalarial, and antipsychotic, antiherpes activities [17]. Fluoroquinolones are well known antibacterial agents and inhibits both bacterial DNA gyrase and topoisomerase IV enzymes, which are members of type II topoisomerases. DNA gyrase catalyzes the negative supercoiling of DNA and is essential for efficient DNA replication, transcription and recombination, while topoisomerase IV is a decatenating enzyme that resolves interlinked daughter chromosomes fol- lowing DNA replication [18, 19]. Based on the hypothesis that these quinolones could also bind to the viral nucleic ac- ids or nucleoprotein-complexes, several quinolone deriva- tives were tested for their antiviral activity and were proven to possess the inhibitory activity against vaccinia, papovavi- ruses, herpes simplex virus type 1 (HSV-1), African swine S. Boyapati