Synthesis, computational studies, antimycobacterial and antibacterial properties of pyrazinoic acid–isoniazid hybrid conjugates

Abstract

Synthesis and computational studies of new pyrazinoic acid–isoniazid hybrid conjugates as potential anti-infective agents.

N-Pyrazinoyl Substituted Amino Acids as Potential Antimycobacterial Agents—the Synthesis and Biological Evaluation of Enantiomers

“…All compounds were tested by the microdilution broth method [58] In previous studies, the activities of the methyl esters of PC-Gly, PC-l-Ala, PC-l-Ser, and PC-l-Tyr against some bacterial strains were evaluated, yet no activity was noted [31], in agreement with the observations in this article. The activities of some free acid compounds reported in the study of Panda et al [33] could be tied to the methodology differences and strain susceptibility, as no activity was seen when corresponding esters were used in our studies. For the full results (Table S4) and methodology, see the Supplementary Material.…”

“…These compounds were more or similarly active at pH 7 compared to isoniazid (INH) (> 70% growth inhibition at 30 µg/mL). However, as a different Mtb strain and methodology was used in the study of Panda et al [33], direct comparison to our study is not applicable. PC-Asp-diEt and some atypical aa derivatives of the structure presented in Figure 1 were tested previously by Kushner et al [30] with no activity, which is in accordance with our results presented in Tables 2 and 3. pH Dependence Based on one of the proposed MoA of our compounds, that is POA-releasing prodrugs, all derivatives were tested at mildly acidic pH 6 as required for the in vitro activity of PZA/POA, and the results were compared to the activities at the commonly used pH 6.6 [22].…”

“…Limited data on similar aa derivatives of PZA are available in the literature. In the work of Panda et al [33], the l-derivatives of non-esterified aa (Leu, Val, allo-Ile, Met, Phe, Trp) were tested. These compounds were more or similarly active at pH 7 compared to isoniazid (INH) (> 70% growth inhibition at 30 µg/mL).…”

“…Up to this point, the only data on the aa derivatives of PZA and their antimycobacterial activity are those found in older research by Kushner et al [30], Badie and Azab [31], and Pinheiro et al [32]. In a very recent study by Panda et al [33], more derivatives of structure presented in Figure 1 were tested on several (myco)bacterial strains showing mild activity at neutral pH. Nevertheless, molecules of the mentioned structure have been tested for their other applications, e.g., as antihistamines [34], insecticides, anthelmintics [35], or proteasome inhibitors [36].…”

An Efficient Greener Approach for N-acylation of Amines in Water Using Benzotriazole Chemistry

“…The amide bond is exceptionally imperative in medicinal chemistry [6][7][8]. Amide groups contribute to the unique properties of peptides, proteins, and numerous other natural and synthetic compounds.…”