Convenient One Pot Synthesis and Antibacterial Evaluation of Some New Mannich Bases Carrying 1,2,4‐Triazolyl Moiety

Abstract

A series of Mannich bases were synthesized by a three-component Mannich reaction. The newly synthesized compounds were well characterized by elemental analyses, IR, NMR and mass spectroscopic studies. The potential antibacterial effects of the synthesized compounds were investigated using standard bacterial strains: Gram-positive and Gram-negative bacteria. Interestingly, all the synthesized compounds were observed to be promising leads, possessing moderate to significant inhibitory activity as compared to standard.

Mannich bases in medicinal chemistry and drug design

“…Furthermore, the replacement of 4-pyridinyl with 2-quinolinyl as substituent at position 5 of the triazole ring, and modification of phenyl into benzyl as substituent at position 4 of the triazole ring led to inactive Mannich bases 133k [176]. Both types of Mannich bases 133l and 134l, featuring a 1,2,4-triazole moiety at position 5 of the triazolethione scaffold, showed good antibacterial activity, but compounds 134l were generally more potent than 133l, and two of candidates 134l actually had MIC values comparable to those of reference drug ciprofloxacin [177]. Mannich bases 133m and 133n [165] were devoid of effective antibacterial activity [178,179], as was structurally related candidate 133o (a singular and notable exception is this compound's activity against Bacillus cereus) [179].…”

“…Out of two synthesized Mannich bases 139o, the candidate having a morpholine residue in the aminomethyl group displayed excellent antimicrobial activity against all the tested microorganisms, while the candidate having a methylpiperazine residue had good or moderate activities against most bacteria in the panel, with the exception of E. coli and K. pneumoniae [190]. The growth inhibition exerted by Mannich bases 139p was moderate compared to reference drugs, and it was uninfluenced by the nature of the amine moiety in the aminomethyl group [177]. Nalidixic acid-based oxadiazolethione Mannich bases 139q exhibited very weak antibacterial activity (MIC values > 750 mg/mL) compared to reference drug streptomycin (MIC ¼ 5 mg/mL), and only towards B. subtilis, but some of the structurally related Mannich bases 140 of 2,3-dihydro-1,3,4-thiadiazole-2-thione ( Fig.…”