Abraham García

The indoles and benzo[c]phenanthridines have attracted much interest as potential anticancer and antibacterial agents. Herein, the synthesis and bioactivity of new and known indole‐coupled dihydrobenzo[c]phenanthridines are reported. Among the investigated compounds, 2j displays potent and selective activity against drug‐resistant Staphylococcus aureus , S. epidermidis , and Enterococcus faecium strains. In addition, 1a‐c and 2a specifically target the multidrug‐resistant Mycobacterium tuberculosis G122, possibly by inhibiting the Pks13 enzyme, as deduced from the in silico analyses. Additionally, compound 1g is more potent than cisplatin against MCF‐7 (breast) and PC‐3 (prostate) human cancer cell lines, whereas 2b is found to be almost as active as cisplatin against PC‐3 and SW‐480 (colorectal) cell lines. Compounds 1a and 1g display remarkable selectivity index values, thus being promising antibacterial and anticancer hits.

The aim of this study was to screen sixteen meso‐1 semi‐synthetic derivatives bearing ether, esther, carbamate, phosphate or aminoether functional groups against five cancer cell lines: MCF‐7 (breast), A549 (lung), HepG2 (liver), HeLa (cervix), and DU145 (prostate) at 25 μM using the MTT assay. Results from the screening showed that two derivatives had the lowest percentage of cell viability at 25 μM, the aminoether derivative meso‐11 and the esther derivative meso‐20 against A549 (44.15±0.78 %) and MCF‐7 (41.60±0.92 %), respectively. Then, it was determined the IC₅₀ value of each compound against their most sensitive cancer cell line. Results showed that aminoether derivative meso‐11 showed potent cytotoxicity against A549 (IC₅₀=17.11±2.11 μM), whereas it resulted more cytotoxic against the LL‐47 lung normal cell line (IC₅₀=9.49±1.19 μM) having a Selective Index (SI) of 0.55. On the other hand, the esther derivative meso‐20 exhibited potent activity against MCF‐7 (IC₅₀=18.20±1.98 μM), whereas it displayed moderate cytotoxicity against the MCF‐10 breast normal cell line (IC₅₀=41.22±2.17 μM) with a SI of 2.2. Finally, studies on the mechanism of action of meso‐20 indicated disruption of MCF‐7 plasma membrane in vitro and the AMPK activation in silico.

Background: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2-related factor 2 (NRF2). Objective and Methods: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. Results and Conclusion: Among the most promising and widely reported metabolites from L. tridentata, are: 3’-demethoxy-6-O-demethylisoguaiacin, 3’-O-methyldihydroguaiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnordihydroguaiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC₅₀), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC₅₀, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4′-trihydroxy-3,7-dimethoxyflavone (EC₅₀, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H₂S/ATP-sensitive potassium channel (K_ATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4′-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4′-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.