Vanessa Pietrowski Baldin1, Regiane Bertin de Lima Scodro2, Mariana Aparecida Lopes-Ortiz3, Aryadne Larissa de Almeida4, Zilda Cristiani Gazim5, Letícia Ferarrese5, Viviane Dos Santos Faiões6, Eduardo Caio Torres-Santos6, Claudia Terencio Agostinho Pires4, Katiany Rizzieri Caleffi-Ferracioli2, Vera Lucia Dias Siqueira7, Diógenes Aparício Garcia Cortez8, Rosilene Fressatti Cardoso7. 1. Programa de Pós-graduação em Biociências e Fisiopatologia, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil. Electronic address: vanessapbaldin@gmail.com. 2. Departamento de Analises Clínicas e Biomedicina, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil. 3. Programa de Pós-graduação em Biociências e Fisiopatologia, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil; Centro Universitário Ingá, Uningá, Rodovia PR 317, 6114, 87035-510 Maringa, Parana, Brazil. 4. Programa de Pós-graduação em Biociências e Fisiopatologia, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil. 5. Laboratório de Química de Produtos Naturais, Universidade Paranaense, Praça Mascarenhas de Moraes, 4282, 87502-210 Umuarama, Parana, Brazil. 6. Laboratório de Bioquímica de Tripanossomatídeos e Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, 4365, 21040-900 Rio de Janeiro, Brazil. 7. Programa de Pós-graduação em Biociências e Fisiopatologia, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil; Departamento de Analises Clínicas e Biomedicina, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil. 8. Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Avenida Colombo, 5790, 87020-900 Maringa, Parana, Brazil.
Abstract
BACKGROUND: The global resurgence of tuberculosis (TB) and the development of drug resistance, as multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis isolates, are a threat to TB control and have created a need for new and more effective anti-TB drugs. AIM: The current study evaluated the in vitro cytotoxicity and activity of Tetradenia riparia essential oil (TrEO) and 6,7-dehydroroyleanone pure compound against M. tuberculosis H37Rv and susceptible and resistant clinical isolates. METHODS: The in vitro activities of TrEO and 6,7-dehydroroyleanone were determined by Resazurin Microtiter Assay Plate (REMA). The cytotoxicity was evaluated in murine peritoneal macrophages by Alamar Blue assay. The cytotoxic effects were expressed as median concentration cytotoxicity (CC50) and the selectivity index (SI) was calculated. RESULTS: TrEO and 6,7-dehydroroyleanone showed activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) 62.5 µg/ml and 31.2 µg/ml, respectively. Both of them exhibited activities against resistant and susceptible M. tuberculosis clinical isolates with MIC values between 31.2 and 62.5 µg/ml. Cytotoxicity assays showed SI 1.9 and 7.9 for TrEO and 6,7-dehydroroyleanone, respectively. CONCLUSION: These results revealed that TrEO isolated from leaves of T. riparia and the pure compound 6,7-dehydroroyleanone display good activity against M. tuberculosis clinical isolates, including MDR isolates, with low cytotoxicity to murine macrophages. The 6,7-dehydroroyleanone compound is a potential candidate for anti-TB drug.
BACKGROUND: The global resurgence of tuberculosis (TB) and the development of drug resistance, as multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis isolates, are a threat to TB control and have created a need for new and more effective anti-TB drugs. AIM: The current study evaluated the in vitro cytotoxicity and activity of Tetradenia ripariaessential oil (TrEO) and 6,7-dehydroroyleanone pure compound against M. tuberculosis H37Rv and susceptible and resistant clinical isolates. METHODS: The in vitro activities of TrEO and 6,7-dehydroroyleanone were determined by Resazurin Microtiter Assay Plate (REMA). The cytotoxicity was evaluated in murine peritoneal macrophages by Alamar Blue assay. The cytotoxic effects were expressed as median concentration cytotoxicity (CC50) and the selectivity index (SI) was calculated. RESULTS:TrEO and 6,7-dehydroroyleanone showed activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) 62.5 µg/ml and 31.2 µg/ml, respectively. Both of them exhibited activities against resistant and susceptible M. tuberculosis clinical isolates with MIC values between 31.2 and 62.5 µg/ml. Cytotoxicity assays showed SI 1.9 and 7.9 for TrEO and 6,7-dehydroroyleanone, respectively. CONCLUSION: These results revealed that TrEO isolated from leaves of T. riparia and the pure compound 6,7-dehydroroyleanone display good activity against M. tuberculosis clinical isolates, including MDR isolates, with low cytotoxicity to murine macrophages. The 6,7-dehydroroyleanone compound is a potential candidate for anti-TB drug.
Authors: Sujogya Kumar Panda; Zilda Cristiani Gazim; Shasank S Swain; Marisa Cassia Vieira de Araujo Bento; Jéssica da Silva Sena; Marie Jeanne Mukazayire; Luc Van Puyvelde; Walter Luyten Journal: Front Pharmacol Date: 2022-06-02 Impact factor: 5.988