# State-of-the-Art and Opportunities for Bioactive Pentacyclic Triterpenes from Native Mexican Plants
## 2 Pentacyclic Triterpenes from Mexican Plants
### Biological Activity Survey of PCTs Found in Mexican Plants
Compounds **(4)** and **(5)** showed an inhibitory activity greater than metronidazoleae (IC\({}_{50}\) 1.23 \(\mathrm{\SIUnitSymbolMicro m}\)) [30]. In another antimicrobial study, the authors isolated two PCTs from Acacia cochiliac-tha and tested its activity against _Staphylococcus aureus_, _Bacillus subtilis_, _Enterococcus ficeum_, _Lactiplantiobacillus plantarumum_, _Escherichia coli_, _Salmonella typhimur  
isoniazid, rifampicin, ethambutol, and streptomycin, respectively. Among all the tested strains, **(14)** had an MIC of 25 \(\upmu\)g/mL, except for streptomycin-monoresistant _M. tuberculosis_, for which the MIC was 12.5 \(\upmu\)g/mL. On the other hand, **(1)** showed the highest MIC at 50 \(\upmu\)g/mL against the multidrug-resistant (H37 Rv) and streptomycin-resistant strains. Additionally, both compounds were applied as a mixture, having an MIC of 12.5 \(\upmu\)g/mL against the H37 Rv strain and an MIC of 25 \(\upmu\)g/mL on the other monoresistant strains. As part of this study, both **(1)** and **(14)** were tested against two clinical isolates: MMDO (resistant to isoniaizid and ethambutol) and MTY 147 (resistant to isoniaizid, rifampicin, ethambutol, and ethionamide), for which **(14)** showed a 25 \(\upmu\)g/mL MIC whereas **(1)** showed an MIC of 50 \(\upmu\)g/mL [33]. Secondly, five non-tuberculosis _Mycobacterium_ species were used for the in vitro activity: _M. chelonae, M. avium, M. fortuitum, M. smegmatis, and M. simiae_. Compound **(1)** and the mixture of both acids had an MIC of 100 \(\upmu\)g/mL on all species, whereas **(14)** showed the same MIC value on the first three species and 200 \(\upmu\)g/mL for the last two species [33]. In addition, the same authors studied the activity of both compounds in a macrophage model considering the H37 Rv strain and the MTY 147 clinical isolate [33]. For this purpose, macrophages (cell line ]774A.1) were infected with both strains separately and treated with several combined ratios of the compounds. After several incubation times (3, 6, 24, and 48 h), the macrophages were lysed in order to measure the intracellular bacillus colony-forming units (CFU) inside them. After 48 h, the mixture (6.25 **(14)** + 12.5 **(1)** mmol/mL) had the highest reduction count (up to 10\({}^{1}\) CFU/mL) on the MDR isolate and the H37 Rv strain (up in the same way as the mixture of 0.625 **(14)** + 1.25 **(1)** on the H37 Rv strain). In this same study, the team infected BALB/c mice with the H37 Rv strain, measuring the bacilli load per lung and the percentage of lung surface area affected by pneumonia after a mixture of both compounds was administered. Briefly, after 60 days of infection, 5 mg/kg of each triterpene was dissolved in ultra-pure olive oil and a total volume of 100 \(\upmu\)L was administered subcutaneously to the mice (proportion 3:1 of **(14)** and **(1)**) 3 times a week for 30 and 60 days [33]. Over time, a decrement in the bacilli load was observed; after 60 days, the charge of the treated mice was approximately 0.1 \(\times\) 10\({}^{6}\) bacilli/lung and near 0.9 \(\times\) 10\({}^{6}\) bacilli/lung in the control mice. For the same period, the percentage of lung surface area affected by pneumonia was 11% and 32% for the treated and control mice, respectively. In the same experiment, the levels of the expression of the genes encoding IFN-\(\upgamma\), TNF-\(\upalpha\), and iNOS were measured, concluding that animals treated with the mixture exhibited higher mRNA expression of IFN-\(\upgamma\) and TNF-\(\upalpha\); however, this was not statistically significant when compared to the control, whereas the iNOS mRNA expression was significantly higher than non-treated animals. Finally, the combination of the triterpene mixture with conventional chemotherapy (10 \(\upmu\)g/kg of rifampicin, 10 \(\upmu\)g/kg isoniaizid, and 30 \(\upmu\)g/kg pyrazinamide)) was analyzed after 7, 14, 30, and 60 days of treatment.