Heteroaromatization of Coumarin Part II: Synthesis, Reactions, Antimicrobial Activities of Novel Pyrido[2,3-d]pyrimidine Derivatives

Abstract

Background: Condensation of 3-acetyl-2H-chromen-2-one (1) with 2‐(4-methoxybenzylidene) malononitrile (2) in ammonium acetate/acetic acid or absolute ethanol/piperidine affords pyridine (3) and chromen-2-one (4) derivatives, respectively. background: Synthesis of a novel series of chromen-3-yl-pyridine derivatives were elucidated using spectroscopic techniques and elemental analysis. antimicrobial activities of compounds were then evaluated in vitro. Compound (E)-3-(3-(4-methoxyphenyl)acryloyl)-2H-chromen-2-one (4), was more effective against all five microorganisms and nicotinonitrile derivative 3 and 1,8-naphthyridin-2-yl)-2H-chromen-2-one derivative 14, while compounds 9, 10a-c, 11, 12 and 13 were moderate activity for antimicrobial activities. Methods: In this study, the reaction of 3 with an electrophilic reagent, namely, formic acid, acetic anhydride and formamide afforded the pyridopyrimidinone and pyridine derivatives (6- 9). Also, treatment of 3 with different aromatic aldehydes, carbon disulfide, NaN3/NH4Cl, 2- (4-methoxybenzylidene)malononitrile and acetophenone afforded pyridopyrimidinone, carbamodithioic acid, tetrazol-5-yl-chromen-2-one, 2H-chromen-2-one, and pyridine derivatives (10-14), respectively. Results: This study synthesized coumarins with antimicrobial activity and verified the structure and purity of the synthesized compounds using spectral data. Conclusion: The new compounds were evaluated in vitro for their antimicrobial activity against gram-positive bacteria (Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus) and gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa), in addition to fungus (Candida albicans). The investigated substances 3 and 14 presented good activity against MRSA, E. coli, P. aeruginosa and C. albicans, while compounds 9, 10a-c, 11, 12 and 13 exhibited good to moderate activity.