Structure–activity Relationship Studies of Microbiologically Active Thiosemicarbazides Derived from Hydroxybenzoic Acid Hydrazides

Abstract

Forty-five derivatives of thiosemicarbazide were synthesized, and their antibacterial activity against Gram-positive and Gram-negative bacteria was evaluated. Some of the described compounds exhibited interesting activity against reference strains of Gram-positive bacteria, whereas only two derivatives had the ability to inhibit the growth of Gram-negative species (Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 13883, Proteus mirabilis ATCC 12453). The most potent antimicrobial activity was observed in the cases of salicylic acid hydrazide derivatives. The differences in activity inspired us to conduct conformational analysis using molecular mechanics level. The obtained results suggest that the molecule geometry, especially at the N4-terminus of thiosemicarbazide skeleton, determines the antibacterial activity. Unfortunately, in opposition to what we expected, only one of the tested compounds inhibited the activity of the topoIV enzyme, and none of them was active against DNA gyrase.

Synthesis and Antibacterial Activity of New Thiazolidine-2,4-dione-Based Chlorophenylthiosemicarbazone Hybrids

“…Summing up, the SARs analysis collectively suggest that at least two different molecular mechanisms of antibacterial activity for TZD-based hybrid compounds are expected. Such observation, however, is not surprising: a similar trend was observed previously for thiosemicarbazide derivatives; one mechanism for their activity was associated with inhibition of bacterial topoisomerases, while the nature of the other is still unrecognized [ 18 , 19 , 21 , 24 , 25 ].…”

“…As we previously reported, substances with an N-N-C(=S)-N structural fragment exhibit antimicrobial activity at low non-toxic concentrations. This activity is similar to or better than reference substances: cefuroxime, ampicillin, and vancomycin [ 17 , 18 , 19 , 20 , 21 ]. Combination of these two mentioned scaffolds in one molecule seems to be a promising “hybrid pharmacophore” approach to new antibacterial agents.…”

“…Hence, we decided to modify initial structures by replacing the azole rings with the chlorophenylthiosemicarbazone fragment. Selection of such substituent was dictated by two factors; as we reported previously, compounds with N-N-C(=S)-N structural motif have the potential to display antibacterial activity at low, non-toxic concentration, similar to or even better than those for standard antibiotics cefuroxime, ampicillin or vancomycin [ 17 , 18 , 19 , 20 , 21 ]. Among them, the best antibacterial response was noted for those with the chlorophenyl substitution ( Figure 1 ) [ 17 ]; the most active compounds had MICs as low as 0.49 mg/L (against Micrococcus luteus and Bacillus subtilis ), making them promising starting structures for the development of new antibacterials.…”

Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids

“…[5]) in alkaline medium. Their chemical structures were confirmed on the basis of 1 H-NMR and 13 C-NMR spectra, and the results of elemental analysis.…”

Synthesis and Antimicrobial Studies of New Trifluoromethylpyrimidine Analogues

“…It is also noticed that the antibacterial activities enhance by the present of 2-thienyl ring at position-4 and this might be based on the fact that 2-thiophene has shown an array of biological activities ranging from antibacterial [20][21][22][23][24], antifungal [25,26], antioxidant [27], and anti-inflammatory activity [28].…”