Bolivia-Kallawayan medicinal plants as leads to anti-HIV, anti-tumor and other potential drugs

Abstract

Drug discovery is a great challenge to scientists to find cures for diseases like AIDS and cancer. Natural products provide very important leads for these drugs. Many successful examples show that traditional medicine plays a key role in drug discovery. Over 1000 years the Kallawaya Indians of Bolivia had discovered about 1000 medicinal plants. Representative samples of these plants have been obtained, taxonomically identified, extracted and tested against HIV, tumors and Mycobacteria. Out of 29 plant species, 5 species were active against HIV; 6 species had anti-tumor activities; 9 species showed anti-leprosy activity, 10 and 7 species inhibited M. tuberculosis and M. avium, respectively. The anti-tumor, tuberculosis and avium active organic extract of Gunnera magellanica, the anti-leprosy aqueous extract of Gunnera magellanica and the anti-HIV aqueous extract of Minthostachys mollis were fractionated by following bioassays. From the organic extract of the anti-HIV and anti-mycobacterium plant Achyrocline satureioides, 5 flavones, [gnaphalin-7-methyl ether ( JQII-92-C ), 3-hydroxyalnetin ( JQII95-C ), 3-methylquercetin ( JQ-92-C ), luteolin ( JQ-92-D ), galangin-3-methyl ether ( JQII-113-A )], one chalcone glycoside, [dehydro-para-asebotin ( JQ-108-G )] and one coumarin [scoparone ( JQ-92-B )] were isolated, identified and their bioactivity determined. From the anti-tumor active plant Polypodium pycnocarpum, six compounds [cycloeucalenol ( JQII-98-C ), ?-sitosterol ( JQII98-E1 ), 24-methylenepollinastanol ( JQII-98-E2 ), 2?, 22-dihydroxy hopane ( JQII-98-G1 ), 6-methoxysterigmatocystin ( JQII-98-G2 ) and 5?, 8?-epidioxyergosta-6, 22-dien-3?-ol ( JQII-98-H )] were isolated and identified by spectroscopic and chemical methods. Nine triterpenoids, sterols and xanthone derivatives were identified only by GC/MS based on a search of the NBS54K mass spectra library. Structure elucidation of the new pentacyclic triterpene 2?, 22-dihydroxyhopane is discussed in detail. It was found that 2?, 22-dihydroxyhopane and 6-methoxysterigmatocystin were responsible for the anti-tumor activity of the plant Polypodium pycnocarpum. Using the anti-HIV active natural product 3,5-dicaffeoylquinic acid as a lead, 3,4-dicaffeoylquinic acid, dicaffeoyl esters of three alkanediols and six cyclohexanediols, 3,5 dicaffeoylbenzoic acid, and L-, D-, and meso-chicoric acid, were synthesized. Only the chicoric acids showed greater anti-HIV activity than the natural product lead. The anti-HIV activity and structure-activity relationships were studied.