New cyclolignans of Larrea tridentata and their antibacterial and cytotoxic activities

• Published in: Phytochemistry letters 2021-06, Vol.43, p.212-218
• Main Authors: Núñez-Mojica, Guillermo, Vázquez-Ramírez, Ana L., García, Abraham, Rivas-Galindo, Verónica M., Garza-González, Elvira, Cuevas González-Bravo, Gabriel E., Toscano, Rubén A., Moo-Puc, Rosa E., Villanueva-Toledo, Jairo R., Marchand, Pascal, Camacho-Corona, María del Rayo
• Format: Article
• Language: English
• Subjects: Antibacterial; Chemical Sciences; Cyclolignan; Cytotoxic; Ecology, environment; Health; Larrea tridentate; Life Sciences; Methylation; Tuberculosis
• ISSN: 1874-3900; 1876-7486
• DOI: 10.1016/j.phytol.2021.04.013

[Display omitted] •Larrea tridentata is a source of new antibacterial and cytotoxic cyclolignans.•Methylation of cyclolignans can enhance the antibacterial and cytotoxic activity.•Drug-resistant gram-positive bacteria is susceptible to cyclolignans antibacterial activity.•Methylated cyclolignans shows antimycobacterial activity against drug-resistant Mycobacterium tuberculosis. From the chloroform extract of Larrea tridentata (Ses. et Moc ex DC.) Coville two new cyclolignans (1 and 2) and six known compounds (3–8) were isolated and characterized. The new compounds were elucidated as 4,4’-dihydroxy-3-methoxy-6,7’-cyclolignan (1) and 3,4-dihydroxy-3’,4’-dimethoxy-6,7’-cyclolignan (2). Compound 1 was methylated to obtain the semi-synthetic derivatives 1a, 1b and, 1c. The structural elucidation of compounds was performed by analysis of 1D and 2D NMR spectral data, HRMS and, X-ray diffraction (compound 1). Antibacterial and cytotoxic activity of compounds was determined against nine clinical isolates of drug-resistant bacteria and two strains of M. tuberculosis (drug-sensitive H37Rv and drug-resistant G122) as well as against three cancer cell lines. Results showed the methylated derivative 1a as the most active antibacterial compound, displaying the best activities against gram-positive bacteria and M. tuberculosis with a minimal inhibitory concentration (MIC) in a range of 6.25–12.5 μg/mL and 12.5−25 μg/mL respectively, having the same activity as the control drug levofloxacin against methicillin-resistant Staphylococcus aureus (MIC 6.25 μg/mL) and linezolid-resistant Staphylococcus epidermidis (MIC 12.5 μg/mL). Cyclolignan 5 was two-fold more active towards (LR) S. epidermidis. Tested compounds were devoid of cytotoxic activity.