The Cytotoxic Cardiac Glycoside (-)-Cryptanoside A from the Stems of Cryptolepis dubia and Its Molecular Targets.

A cardiac glycoside epoxide, (-)-cryptanoside A (1), was isolated from the stems of Cryptolepis dubia collected in Laos, for which the complete structure was confirmed by analysis of its spectroscopic and single-crystal X-ray diffraction data, using copper radiation at a low temperature. This cardiac glycoside epoxide exhibited potent cytotoxicity against several human cancer cell lines tested, including HT-29 colon, MDA-MB-231 breast, OVCAR3 and OVCAR5 ovarian cancer, and MDA-MB-435 melanoma cells, with the IC50 values found to be in the range 0.1-0.5 µM, which is comparable with that observed for digoxin. However, it exhibited less potent activity (IC50 1.1 µM) against FT194 benign/nonmalignant human fallopian tube secretory epithelial cells when compared with digoxin (IC50 0.16 µM), indicating its more selective activity toward human cancer versus benign/nonmalignant cells. (-)-Cryptanoside A (1) also inhibited Na+/K+-ATPase activity and increased the expression of Akt and the p65 subunit of NF-κB but did not show any effects on the expression of PI3K. A molecular docking profile showed that (-)-cryptanoside A (1) binds to Na+/K+-ATPase, and thus 1 may directly target Na+/K+-ATPase to mediate its cancer cell cytotoxicity.

Three promising antimycobacterial medicinal plants reviewed as potential sources of drug hit candidates against multidrug-resistant tuberculosis.

Regimens of current drugs for tuberculosis are lengthy and are associated with many adverse effects. Currently, the emergence of different resistant strains has been observed. This urges a need for the discovery and development of novel drugs. The main sources of drug lead candidates are based on natural products. Zanthoxylum leprieurii, Lantana camara, and Cryptolepis Sanguinolenta are among the plants that have antimycobacterial activity. Recent technological methods, such as metabolomics, can rapidly detect and identify active compounds from medicinal plants. In this review, we aim to provide an overview and discussion of the antimycobacterial activity, phytochemical analysis and toxicity profile of these plants and their products as well as the potential of metabolomic fingerprinting of medicinal plants with a given activity on microbes, in the search for the potential drug hit molecules. The information for this review was extracted from databases such as Excerpta Medica Database, Google Scholar, Springer, and PubMed Central. Primary studies, using a combination of the keywords antimycobacterial medicinal plant, multidrug-resistant tuberculosis, phytochemistry, toxicity, Zanthoxylum leprieurii, Lantana camara, Cryptolepis sanguinolenta, and plant metabolomics/metabolic fingerprinting of plant extracts, have been considered. The above-mentioned plant species showed antimycobacterial activity against drug-resistant strains of M. tuberculosis. They may provide potential candidates for novel drugs against multidrug-resistant tuberculosis. However, extensive work is still needed. To our knowledge, there is no or limited literature that reports the metabolic fingerprints of these plants. The analysis of the metabolite fingerprints of medicinal plants with similar antimicrobial activity could be important to determine whether the activity results from common metabolites within different plant species. This review shows that these plants are potential candidates to provide drug hits against multidrug-resistant tuberculosis strains. Future studies of compound optimization, in vivo safety and efficacy, as well as of the specific mechanisms of action are however required.