Synthesis, antimicrobial activity, and molecular docking studies of new fused pyrimidinethiones

Abstract

2‐Cyano‐3‐(methylsufany)‐3‐(phenylamino)prop‐2‐enethioamide (3) was treated with dimethylformamide‐dimethylacetals (DMF‐DMA), dimedone, isatin, and/or 3‐iminobutanenitrile to give prop‐2‐enethioamide 4, N‐substituted thioamides 9, 10, and 5,6‐dihydropyridine 12, respectively. While, the reaction of bis‐thioamide 5 with DMF‐DMA gave 4‐thioxo‐1,4‐dihydropyrimidine 6. Cyclization of compound 4 using different conditions afforded pyrimidinethione 15, which reacted with guanidine, cyanothioacetamide, and/or 2‐cyanomethylpyrazole to yield the corresponding fused pyridopyrimidine 17 and pyrimidopyrimidines 18 and 20, respectively. Structures of the newly compounds were characterized by using their infrared (IR), nuclear magnetic resonance (NMR) data and elemental analysis. The synthesized compounds were in vitro evaluated for their antibacterial activity through the zone of inhibition measurement. The results revealed promising antibacterial activity for compounds against the used pathogenic bacterial strains. Moreover, the antibacterial activity of the active compounds (4, 6, 9, 10, 12, 15, 17, 18, and 20) was interpreted using molecular docking against E. coliFabH‐CoA complex (PDB ID: 1HNJ) to determine the binding energy, binding interactions, and molecules' orientations inside the active site of the target protein.

A review on pyrimidine‐based derivatives: Synthesis and their biological application

“…These findings collectively suggest compound 23 has emerged as a potential anti-inflammatory agent with minimal ulcerogenic activities. Hussien investigated antibacterial activity for several pyrimidine compounds 50(a-e) against different strains of gram-positive (B. subtilis, S. aureus), Gram-negative (E. coli, P. aeruginosa), and two fungal strains (C. albicans and A. Niger) (Figure 10) [47]. The activity was assessed at a 10 mg/mL concentration and dissolved in DMSO.…”

“…These interactions are essential for the proper functioning of nucleic acids, the transmission of genetic information, and a wide range of other cellular processes (Figure 3) [46]. Additionally, pyrimidine derivatives have a wide range of biological properties in the therapeutic industry, including antimicrobial [47], antibacterial [48], antifungal [49], anti‐inflammatory [50], antitumor [8], anticancer [51], antioxidant [52], antihypertension [53], anti‐HIV [54], antimalarial [55], antiviral [56], insecticide [57], antiplasmodial [58] activities.…”