Samija Muratović

Benzylidene-bis-(4-Hydroxycoumarin) and Benzopyrano-Coumarin Derivatives: Synthesis, 1H/13C-NMR Conformational and X-ray Crystal Structure Studies and In Vitro Antiviral Activity Evaluations

We report on the synthesis of 4-hydroxycoumarin dimers 1–15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16–20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The chemical identities and structure of compounds 1–20 were deduced from their homo- and heteronuclear NMR measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1D difference NOE enhancements. Unequivocal proof of the stereostructure of compounds 7, 9, 16 and 18 was obtained by single crystal X-ray diffraction method. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyl- and 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. Consequently, the compounds 7 and 9 adopt conformations in which two 4-hydroxy-coumarin moieties are anti-disposed. Antiviral activity evaluation results indicated that the 4-bromobenzylidene derivative of bis-(4-hydroxycoumarin) (compound 3) possesses inhibitory activity against HSV-1 (KOS), HSV-2 (G), vaccinia virus and HSV-1 TK- KOS (ACVr) at a concentration of 9–12 μM and at a minimum cytotoxic concentration (MCC) greater than 20 μM. Compounds 4–6, 8, and 20 were active against feline herpes virus (50% effective concentration, EC50 = 5–8.1 μM), that is at a 4-7-fold lower concentration than the MCC.

Artificial Neural Network and Docking Study in Design and Synthesis of Xanthenes as Antimicrobial Agents

The aim of the study was to investigate the efficiency of artificial neural networks and docking studies in prediction of antimicrobial activity for new compounds. For that purpose, two multilayer neural networks with feedforward architecture were developed. Also, docking studies were performed to investigate the hypothetical binding mode of the target compounds. A series of 2,2,5,5-tetramethyl-9-aryl-3,4,5,6,7,9-hexahydro-1H-xanthen-1,8(2H)-dione derivatives have been previously synthesized, characterized and evaluated for in vitro antimicrobial activity against Escherichia coli and Candida albicans strains. By comparing results of in vitro investigation, new 2,2,5,5-tetramethyl-9-(3,5-dibromophenyl)-3,4,5,6,7,9-hexahydro-1H-xanthen-1,8(2H)-dione possessed better antimicrobial activity against tested microorganisms than previously synthesized derivatives and these results also correlated well with results of docking studies.