Preclinical Evaluation of Selene-Ethylenelacticamides in Tuberculosis: Effects Against Active, Dormant, and Resistant Mycobacterium Tuberculosis and In Vitro Toxicity Investigation

Microorganisms, Journal Year: 2025, Volume and Issue: 13(2), P. 396 - 396

Published: Feb. 11, 2025

Selene-ethylenelacticamide derivatives have been suggested as promising scaffolds with leishmanicidal activity. In this work, we demonstrated, for the first time, effectiveness of selene-ethylenelacticamide against mycobacteria. Firstly, selene-ethylenelacticamides inhibited growth laboratory strains Mycobacterium tuberculosis MIC values ranging from 10 to 20 µM. Importantly, three were active two multi-drug-resistant clinical isolates M. similar pan-sensitive strains. addition, NC31 and NC34 displayed an improved activity compared group treated isoniazid in six-week nutrient-starved cultures. Moreover, toxicity studies, did not significantly affect viability both Vero E6 HepG2 cell lines. Artemia salina nauplii survival at concentrations lower than 100 a synergistic effect when combined rifampicin. Molecular docking simulations used evaluate DprE1 dihydrofolate reductase enzymes putative targets selene-ethylenelacticamides, mechanisms that could contribute antitubercular Our findings reveal may represent hit further drug optimization future preclinical development new anti-mycobacterial agent, especially cases resistant and/or dormant forms tuberculosis.

Language: Английский

Host-Mediated Antimicrobial Effects and NLRP3 Inflammasome Modulation by Caulerpin and Its Derivatives in Macrophage Models of Mycobacterial Infections

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 561 - 561

Published: March 1, 2025

Caulerpin, a bis-indole alkaloid isolated from Caulerpa racemosa, has several documented pharmacological activities, including antineoplastic and antiviral properties. This study aimed to evaluate the anti-inflammatory anti-tubercular potentials of caulerpin its analogues in RAW 264.7 macrophages infected with Mycobacterium spp. Additionally, we evaluated cytokine production NLRP3 expression this infection model. Toxicity tests were performed using Vero E6 HepG2 cell lines Artemia salina. Pre-incubation cells decreased internalized M. smegmatis tuberculosis H37Ra. Furthermore, treatment smegmatis-infected reduced bacterial loads. Caulerpin CFU count bacilli H37Ra In addition, diethyl derivative notably found modulate IL-1β TNF-α model after quantifying pro-inflammatory cytokines NLRP3. derivates did not affect viability or nauplii survival toxicity studies. These findings demonstrate that exhibit activity against show promising potential for further efficacy safety evaluation.

Language: Английский