Tyrianthinic Acids from Ipomoea tyrianthina and Their Antimycobacterial Activity, Cytotoxicity, and Effects on the Central Nervous System # Ismael Leo ´n-Rivera,* ,† Gumersindo Miro ´n-Lo ´pez, † Gloria Marı ´a Molina-Salinas, ‡ Maribel Herrera-Ruiz, § Samuel Estrada-Soto, ⊥ Marı ´a del Carmen Gutie ´rrez, | Daniel Alonso-Cortes, § Gabriel Navarrete-Va ´zquez, ⊥ Marı ´a Yolanda Rı ´os, † and Salvador Said-Ferna ´ndez ‡ Centro de InVestigaciones Quı ´micas, UniVersidad Auto ´noma del Estado de Morelos, AVenida UniVersidad 1001, Col. Chamilpa 62209 CuernaVaca, Morelos, Me ´xico, Centro de InVestigacio ´n Biome ´dica del Noreste, Instituto Mexicano del Seguro Social, San Luis Potosı ´ y Dos de Abril, Col. Independencia 64720 Monterrey, NueVo Leo ´n, Me ´xico, Centro de InVestigacio ´n Biome ´dica del Sur, Instituto Mexicano del Seguro Social, Argentina 1 Col. Centro Xochitepec, Morelos, Me ´xico, Facultad de Farmacia, UniVersidad Auto ´noma del Estado de Morelos, AVenida UniVersidad 1001, Col. Chamilpa 62209 CuernaVaca, Morelos, Me ´xico, and Centro de InVestigacio ´n en Biotecnologı ´a, UniVersidad Auto ´noma del Estado de Morelos, AVenida UniVersidad 1001, Col. Chamilpa 62209 CuernaVaca, Morelos, Me ´xico ReceiVed April 30, 2008 Four new partially acylated tetrasaccharides of 11-hydroxyhexadecanoic acid (1-4) were isolated from a methanolic extract of Ipomoea tyrianthina. The structures of these compounds were elucidated by spectroscopic and chemical methods. The resin glycoside composition of I. tyrianthina varied with the location of growth in Mexico. Compounds 1-4 showed antimycobacterial activity, were cytotoxic against the KB cell line, and, in a mouse model, exhibited potentiation of hypnosis induced by pentobarbital, protected against seizures induced by pentylenetetrazole, and released GABA and glutamic acid. Ipomoea tyrianthina Lindley (syn. Ipomoea orizabensis Pelletan, Lebed. ex Steud., Convolvulaceae) is a twining herb with large roots that has been used mainly as a purgative since prehispanic times. The chemical components of the glycoresin obtained from the root of this plant have been characterized as tetrasaccharides of jalapinolic acid. 1-3 It has been shown that the growing location affects the chemical composition of the glycoresin in Ipomoea species. 3 Tuberculosis (TB) is still a major cause of death all over the world. There were an estimated 8.8 million new TB cases in 2005, and 1.6 million people died, including 195 000 patients infected with HIV/AIDS. When considered along with the emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MDR- TB), the magnitude of the problem becomes clear, as it will become inevitably even more difficult to treat TB in developing countries in particular. 4 The need for new drugs to extend the variety of TB drug options is urgent. New chemical entities with novel mecha- nisms of action should possess activity against MDR-TB. There are some reports of Mexican plants with ethnomedicinal use against respiratory infections or related conditions that have been shown to be sources of antitubercular compounds. 5-8 The antimycobac- terial activities of glycolipids have been reported by Barnes et al., using a crude extract of Ipomoea leptophylla 9 and of some macrolactone tetrasaccharide glycolipids isolated from Ipomoea tricolor by Rivero-Cruz et al. 10 More recently, crypthophilic acids A-C were examined in vitro as potential antimycobacterial substances. 11 The roots of I. orizabensis have been also used to treat epilepsy. 12 In a previous report, we have described the antidepressant and protective effects against pentylenetetrazole-induced seizures by tetrasaccharide glycolipids purified from a dichloromethane extract of I. tyrianthina. 3 Similar effects on the central nervous system (CNS) have been reported by Herrera-Ruiz et al., as a result of the administration of an ethyl acetate extract from the roots of Ipomoea stans. 13 The molecular structures of compounds 1-4 are very similar to those of the glycolipids isolated from I. tyrianthina 3 and I. stans 13 that have exhibited activity on the CNS of mice. The above-mentioned data suggested the possibility that tyrianthinic acids (1 and 2) are able to induce effects on the CNS of mice. In a continuing investigation on secondary metabolites with biological activity from Ipomoea species, we have studied the resin glycosidic content of the methanolic extract from the roots of I. tyrianthina collected in three different regions of Mexico. We report herein on the isolation and characterization of four new partially acylated tetrasaccharide resin glycosides (compounds 1-4) from the methanolic extract of I. tyrianthina, as well as their antimyco- bacterial activity, cytotoxicity in four cell lines, and effects on the CNS. Results and Discussion The roots of I. tyrianthina were dried, pulverized, defatted with hexane, and macerated succesively in dichloromethane and metha- # This work was taken in part from the Ph.D. thesis of G. Miro ´n-Lo ´pez. * To whom correspondence should be addressed. Tel: (+52) 777 329 79 97. Fax: (+52) 777 329 79 98. E-mail: ismaelr@ciq.uaem.mx. † Centro de Investigaciones Quı ´micas, Universidad Auto ´ noma del Estado de Morelos. ‡ Centro de Investigacio ´n Biome ´dica del Noreste, Instituto Mexicano del Seguro Social. § Centro de Investigacio ´n Biome ´dica del Sur, Instituto Mexicano del Seguro Social. ⊥ Facultad de Farmacia, Universidad Auto ´noma del Estado de Morelos. | Centro de Investigacio ´n en Biotecnologı ´a, Universidad Auto ´noma del Estado de Morelos. J. Nat. Prod. 2008, 71, 1686–1691 1686 10.1021/np800266a CCC: $40.75  2008 American Chemical Society and American Society of Pharmacognosy Published on Web 10/01/2008