Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents

Abstract

Several thieno[2,3-d]pyrimidinediones have been synthesized and examined for antibacterial activity against a range of Gram-positive and Gram-negative pathogens. Two compounds displayed potent activity (2–16 mg/L) against multi-drug resistant Gram-positive organisms, including methicillin, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus (MRSA, VISA, VRSA) and vancomycin-resistant enterococci (VRE). Only one of these agents possessed moderate activity (16–32 mg/L) against Gram-negative strains. An examination of the cytotoxicity of these agents revealed that they displayed low toxicity (40–50 mg/L) against mammalian cell and very low hemolytic activity (2–7%). Taken together, these studies suggest that thieno[2,3-d]pyrimidinediones are interesting scaffolds for the development of novel Gram-positive antibacterial agents.

Antimicrobial activities and mode of action of the selected novel thienopyrimidines derivatives 2-[2-(diphenylmethylene) hydrazino]-5-isopropyl-3-methylthieno [2, 3-d] pyrimidin-4-one

“…Thus, the ultimate goal of study the mechanisms of action of antimicrobial compounds will help to improve the bactericidal activity of a product, to confirm that biocides are employed in the most advantageous manner and to ensure the prevention of the emergence of microbial resistance. Furthermore, understanding the target sites of the antimicrobial compounds will lead to improved antimicrobial formulations (11,1). references…”

“…and cephalosporin-resistant Streptococci has had a major impact on infections in both the hospital and community setting (1). Thus, there is a pressing need for new efficacious antimicrobial agents that are capable of treating resistant bacterial strains.…”

“…In spite of the enormous antimicrobial activity of thienopyrimidines compounds and their derivatives that have been discovered, the mechanisms of action of these compounds are not yet reported (1). According to the reports of antimicrobial activity for structurally unrelated thienopyrimidinones, the biocides and antibiotics have multiple target sites within the microbial cell and the overall damage to these target sites results in the bactericidal effect.…”

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“…[1][2][3][4][5][6][7][8][9] Among all the heterocyclic derivatives, the class of multicycle compounds bearing thienopyrimidine nucleus exhibit a diversity of pharmacological effects such as antibacterial, antifungal, kinase inhibition, immunosuppressive, antidiabetic and anticancer activity .Up to now, there are many different structures containing thienopyrimidine nucleus have been synthesized and evaluated for biological activities. [10][11][12][13][14][15][16][17] Similarly, the Shiff bases have also been reported to possess an array of biological activities namely antimicrobial, ulcerogenic, anti HIV, anticonvulsant, and CNS depressant activities [18][19][20][21] The promising bioactive diversity of these class of heterocyclic compounds and Schiff bases urged us to synthesize and biologically evaluate a series of novel structural variants of thieno [2, 3-d] pyrimidinone derivatives. We have synthesized and utilized 3-amino 2-methyl 4, 5-tetramethylene thieno [2, 3-d] pyrimidin (3H)-4-one as key prototype structural unit, and treated the 3-active amino group with substituted aryl aldehydes to get a new series of Schiff bases.…”

Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives

“…Furthermore, thieno [2,3-d]pyrimidine derivatives show antibacterial (6) and antiproliferative activity (7). Also, chromene--3-carboxamide acts as an anti-Helicobacter pylori agent (8) and pyrazole derivatives have a specific effect with favorable antitumor activity (9).…”