Drug lead discovery through plant bioprospecting in Latin America

Abstract

The bioassay guided fractionation of two Latin American plants, structure elucidation of pure isolates, and LC/MS studies of six plant extracts is presented here along with the structure determination of two compounds using X-ray diffraction. The bioassay guided fractionation of the antibacterial and antitubercular CH2Cl2-MeOH extracts of the Argentinean plant Caiophora coronata Hook. et Arn. (Loasaceae) and the Chilean plant Myrcianthes coquimbensis (Barn.) Landrum et Grifo (Myrtaceae) respectively led to the isolation and complete structure elucidation of nine compounds from the active fractions. Three of these isolates were determined to be new. Namely, a new triterpene, 1beta,3beta-dihydroxyurs-12-en-27-oic acid, a new iridoid, 1alpha-methoxy-6alpha,10-dihydroxyisoepiiridomyrmecin (caiophoraenin) from C. coronata and a new monoterpene (1S,3 S,4R)-1-methyl-4-(1-methylethenyl)-1,3-cyclohexanediol from M. coqumibensis. All chemical structures were established unequivocally by physical and spectroscopic techniques including-melting point, optical rotation, 1D and 2D NMR, HR-FABMS, and FT-IR. Absolute configuration of the new monoterpene was established by Mosher's esterification. The antibacterial activity of all isolates from C. coronata were determined against methicillin-sensitive (MSSA) and -resistant (MRSA) strains of Staphylococcus aureus, Bacillus subtilis (BS), vancomycin-resistant Enterococcus faecium (VREF), Escherichia coli (EC), E. coli imp (ECimp), and Candida albicans (CA). 1beta,3beta-Dihydroxyurs-12-en-27-oic acid was found active against BS, MSSA, MRSA, VREF, and ECimp with MIC values of 2, 4, 4, 4 and 16 mug/ml respectively, whereas, other isolates were essentially inactive. The antitubercular activity of all isolates from M. coquimbensis was evaluated against M. tuberculosis using the microplate alamar blue assay. Oleanolic acid was determined to be the active principle of the extract with an MIC value of 29.66 mug/mL whereas other isolates were regarded as inactive (MIC > 128 mug/mL). Chemical investigations by LC/MS of species closely related to C. coronata and M. coquimbensis were also conducted. Structure solutions by single crystal X-ray crystallography, of an iridoid (4R,5R,7S,8S,9 S)-(-)-7-hydroxy-8-hydroxymethyl-4-methylperhydrocyclopenta[ c]pyran-1-one, and a fernane (3R,5S,9 R,10S,13S,14S,17 R,18R,21R)-(-)-fern-7-ene-3alpha-ol, isolated from the antitubercular methanolic extracts of Valeriana laxiflora DC (Valerianaceae) and Sebastiania brasiliensis Spreng. (Euphorbiaceae) respectively is also presented. The absolute configuration of these compounds was also determined.