Antituberculosis Activities of Lapachol and β-Lapachone in Combination with Other Drugs in Acidic pH.

Autor:	Ieque AL; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Brazil., Carvalho HC; Postgraduate Program in Biosciences & Physiopatology, State University of Maringá, Maringá, Brazil., Baldin VP; Postgraduate Program in Biosciences & Physiopatology, State University of Maringá, Maringá, Brazil., Santos NCS; Postgraduate Program in Biosciences & Physiopatology, State University of Maringá, Maringá, Brazil., Costacurta GF; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Brazil., Sampiron EG; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Brazil., Fernandez de Andrade CMM; Postgraduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Brazil., Siqueira VLD; Postgraduate Program in Biosciences & Physiopatology, State University of Maringá, Maringá, Brazil., Caleffi Ferracioli KR; Postgraduate Program in Biosciences & Physiopatology, State University of Maringá, Maringá, Brazil., Cardoso RF; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Brazil.; Postgraduate Program in Biosciences & Physiopatology, State University of Maringá, Maringá, Brazil., Cortez DAG (in memoriam); Postgraduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Brazil., Silva EL; Department of Chemistry, State University of Maringá, Maringá, Brazil., Scodro RBL; Postgraduate Program in Health Sciences, State University of Maringá, Maringá, Brazil.
Jazyk:	angličtina
Zdroj:	Microbial drug resistance (Larchmont, N.Y.) [Microb Drug Resist] 2021 Jul; Vol. 27 (7), pp. 924-932. Date of Electronic Publication: 2020 Sep 01.
DOI:	10.1089/mdr.2020.0164
Abstrakt:	Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) is a challenge to be overcome. The increase of resistant isolates associated with serious side effects during therapy leads to the search for substances that have anti-TB activity, which make treatment less toxic, and also act in the macrophage acidic environment promoted by the infection. Objective: The aim of this study was to investigate lapachol and β-lapachone activities in combination with other drugs against Mycobacterium tuberculosis at neutral and acidic pH and its cytotoxicity. Design: Inhibitory and bactericidal activities against M. tuberculosis and clinical isolates were determined. Drug combination and cytotoxicity assay were carried out using standard TB drugs and/or N -acetylcysteine (NAC). Results: Both naphthoquinones presented activity against MDR clinical isolates. The combinations with the first-line TB drugs demonstrated an additive effect and β-lapachone+NAC were synergic against H 37 Rv. Lapachol activity at acidic pH and its association with NAC improved the selectivity index. Lapachol and β-lapachone produced cell morphological changes in bacilli at pH 6.0 and 6.8, respectively. Conclusion: Lapachol revealed promising anti-TB activity, especially associated with NAC.
Databáze:	MEDLINE
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