Month 2019 Design and Synthesis of Novel C 4 -Linked Substituted 2H-Chromen-2-one- hypoxanthine Hybrids as Potential Antimicrobial Agents: An Approach to Molecular Docking Studies Soniya D. Naik and Kallappa M. Hosamani* Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India *E-mail: dr_hosamani@yahoo.com Received May 20, 2018 DOI 10.1002/jhet.3432 Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com). We present here design and synthesis of very efficient, high-yielded and simple approach of a series of C 4 - linked coumarin–hypoxanthine pharmacophores 1(a–j) with moderate to excellent in vitro antimicrobial ac- tivity. According to earlier studies, potential modification at C 4 -position of coumarin ring provided excellent bioactive molecules. All the titled compounds were characterized by spectroscopic and elemental analyses. Titled compounds have been developed via systematic tuning of coumarin ring substitutions, which are pre- pared from the well-known Pechmann condensation reaction. The addition of a pendent nucleobase in hypo- xanthine group improved the in vitro antimicrobial activity. Computational studies were also mimicking the potent biomolecules. A good pharmacokinetic profile is suggested by theoretical calculation of absorption, distribution, metabolism, and excretion properties. Therefore, synthesis of these titled compounds provided an insight towards better antimicrobial agents. J. Heterocyclic Chem., 00, 00 (2019). INTRODUCTION In spite of the remarkable improvement in medicine, treatment of infectious diseases is still a serious concern to the clinics because of disclosure of multidrug resistance in most of the pathogens [1,2]. Annually, 57 million deaths occur globally because of infectious diseases alone, and the number is likely to rise in the coming years as said by the World Health Organization. Great challenge in almost all the clinics is posed by multidrug-resistant pathogens because of their capability of escaping from lethal action of existing antimicrobial agents, which cause nosocomial infections [3]. Each year, about 2 million people come with bacterial disease in hospitals around the world; now 70% of cases include strains that are unaffected by the least one drug [4]. In addition, the failure of selective activity of antifungal drugs is due to the biochemical equivalence between fungi forms and human cell, and the leading problem we experience with this is easily getting resistance in developing secure and effective antifungals. Clinical value of current antifungal agents has been limited by the elevated threat of harmfulness and pharmacological deficiencies of the compounds. Therefore, there is still an existing need for the broad spectrum of antibacterial and antifungal compounds [5–7]. Significant investment and exploration in the area of heterocyclic compounds as anti-infectives are now critically needed if a public health emergency is to be prevented [8]. Several oxygen-containing heterocyclic structures such as coumarin derivatives were associated with the benzopyrone family. Coumarin compounds contributed an extended therapeutic outline with a wide range of biological activities, which are naturally plant-derived or synthetically obtained substances [9]. Almost all coumarin derivatives have been considered as the key subunits for different kinds of effective drug candidates in terms of their dynamic pharmacological activities such as anti-inflammatory [10], antitubercular [11], anti-human immunodeficiency virus [12], antioxidant [13], anticoagulant [14], anticancer [15], and antiviral [16]. In addition, these derivatives are used as pharmaceuticals and optical brighteners [17], additives in foods and cosmetics [18], and laser dyes [19]. Some of the established coumarin skeletons containing antimicrobials are novobiocin and chlorobiocin, which are identified as potent inhibitors of bacterial DNA gyrase (I and II, Figure. 1) [20–22]. Potential modification at C 4 -position of coumarin pharmacophore with some heterocyclic moieties such as thiadiazole, trizole, and benzamide significantly enhances the antimicrobial activity and broadens their antimicrobial efficiency (III–V, Figure. 1) © 2019 Wiley Periodicals, Inc.