Synthesis, Structural Elucidation of Novel Thieno [2,3-d] Pyrimidine Core Unit Containing 1,2,4-Triazoles and Thiophenes as Potent Antimicrobial Activity

Prabhakar, V.; Kondra, Sudhakar Babu; Maddula, Srinivasula Reddy

doi:10.4172/2161-0401.1000169

Cited by 5 publications

(1 citation statement)

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“…Other reports have shown some examples of successful modifications of other positions of the thieno [2,3-d]pyrimidine system as well as fusion of this ring system with different heterocycles (which led to the effective antimicrobials). The examples tetrahydrobenzo [4,5]thieno [2,3-d]pyrimidine derivatives [12,13], 5-furyl [14] and 2-thienyl theinopyrimidines fused with triazole [15] or pyrimidine cycles can also be mentioned [16].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and In Vitro Antimicrobial Activity of 6-(1H-Benzimidazol-2-yl)-3,5-dimethyl-4-oxo-2-thio-3,4-dihydrothieno[2,3-d]pyrimidines

et al. 2021

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The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitor’s binding site according to the docking studies results.

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