1,2,4‐Triazole and benzimidazole fused dihydropyrimidine derivatives: Design, green synthesis, antibacterial, antitubercular, and antimalarial activities

Abstract

This study reports the design and synthesis of novel 1,2,4-triazolo/benzimidazolopyrimidine linked 1-benzyl-4-[(p-tolyloxy)methyl]-1,2,3-triazole derivatives as potent antimicrobial agents according to their in vitro antibacterial, antifungal, antitubercular as well as antimalarial activities. An efficient, ecologically benign, and facile multicomponent synthesis was employed to synthesize these derivatives. The synthesis is accelerated with the mild and eco-friendly organocatalyst tetrabutylammonium bromide, providing a yield of 82%-96% within the short reaction time of 0.5-1.5 h. Compared with the MIC values of ciprofloxacin and ampicillin on the respective strains, compound d2 showed better activity against Escherichia coli and Streptococcus pyogenes and compound d8 showed better MIC against Staphylococcus aureus. Additionally, compounds d3, d4, and d5showed potent MIC values against Pseudomonas aeruginosa. All triazolo-pyrimidine derivatives d1-d8 showed potent inhibitory action against Gram-positive strains.Compound e3 showed good potency against Mycobacterium tuberculosis H37Rv. The IC 50 values of d3 and e2 indicated better activity against Plasmodium falciparum.Collectively, these derivatives depict potent multifaceted activity and provide promising access for further antimicrobial and antimalarial investigations.

Dihydroazolopyrimidines: Past, Present and Perspectives in Synthesis, Green Chemistry and Drug Discovery

“…). [234] Mokariya et al [235] showed a possibility of using tetrabutylammonium bromide (TBAB) as catalyst in an efficient, sustainable green and high-yielding multicomponent treatment of 2-aminobenzimidazole 135 with 4-[(1-benzyl-1H-1,2,3triazol-4-yl)methoxy]benzaldehyde 148 and acetoacetanilide derivatives 51 in aqueous ethanolic solution (1 : 1) leading to the formation of dihydrobenzo [4,5]imidazo[1,2-a]pyrimidine carboxamide derivatives 149 (Scheme 58).…”

“…[316] From the series of 4,7-dihydro-1,2,4-triazolo [1,5a] ). [235] 5-(Furan-2-yl)-7-(thiophen-2-yl)-4,7-dihydrotetrazolo[1,5a]-pyrimidine 257 was the most active compound against E. coli (MIC = 50 μg/mL) and L. monocyutogenes (MIC = 100 μg/mL) from the series of 1,4-dihydroazolopyrimidines obtained by cyclocondensation of various aminoazoles with 1-(furan-2-yl)-3-(thiophen-2-yl)-propen-1-one. Docking results indicate that this compound is able to bind efficiently to the active site of DNA gyrase.…”

“…Antitubercular activity against the most studied MTB H37Rv was found in the above series of compounds 255 a (R = 4-F, MIC = 93 μM) 256 a,b (R = 4-F and 4-CF 3 , MIC = 85 and 39 μM, respectively). [235] Dihydro-1,2,4-triazolo[1,5-a]pyrimidines with pyrazole substituents at the C-7 atom in pyrimidine ring 258 a,b were selected from a series of 30 related compounds on the basis of in vitro antitubercular activity and cytotoxicity against the H37Rv strain of MTB. These substances showed moderate activities (MIC = 0.39 and 0.78 μg/mL, respectively) compared with isoniazid and rifampicin (MIC = 0.30 and 0.50 μg/ mL, respectively).…”

“…Triazolpyrimidine derivative 255 b (R=4‐CF 3 , IC 50 =0.82 μM) and pyrimidobenzimidazole 256 a (R=4‐F, IC 50 =0.99 μM) were superior to the reference drug quinine (IC 50 =2.71 μM) in terms of the level of antiparasitic activity against P. falciparum . Remarkable antifungal properties against C. albicans have been found in compounds 255 a , c , e (R=H, 4‐F, 4‐Cl, 4‐Me) and 256 b (R=4‐CF 3 ) [235] …”

Design and Synthesis of Antifungal Candidates Containing Triazole Scaffold from Natural Rosin against Valsa mali for Crop Protection

“…Nitrogen-containing heterocyclic compounds with high biological activities are considered as important pharmaceutical or pesticide intermediates. , Among them, triazole compounds that contain a high electron cloud density at the three N atoms of their rings also have high antifungal, insecticidal, herbicidal, and other agricultural biological activities. , Since Bayer AG reported the first commercial triazole fungicide-triazolone in 1973, triazole scaffolds have become widely used as pesticides. − In addition, thiophene heterocycle and a Schiff-based group are reported to have extensive antifungal activities, as thiophene heterocycle contains a S atom and the Schiff-based group (CN) contains N atoms; both S and N atom contain lone pair electrons, which can easy to form interactions with amino acid residues, resulting in lethal effect. − …”