Chemical investigation of the bieactive plants: achyrospermum carvalhii, hoslundia opposita and lettowian thusstellatus

This thesis reports on the chemical investigations of the root and stem barks of two bioactive plants of the family Lamiaceae, Achyrospermum carvalhii Gurke and Hoslundia oppositaVahl and that of Lettowian thusstellatus Diels, which belongs to the family Annonaceae. In these investigations, a novel A-ring contracted ursolic acid derivative, 1-benzoyloxyhyptadienic acid and three other known terpenoids 3-O-benzoylhosloppone, betulinic and oleanolic acids were isolated from the root bark of H opposita. A mixture of 3-O-benzoylhosloppone and 3-O-benzoyl-5,b-dihydrohosloppone were also obtained from the root bark. 3-O-Benzoylhosloppone and 1-benzoyloxyhyptadienic acid exhibited strong antimalarial activity against the multidrug resistant k1 strain of Plasmodium falciparum malaria parasites in vitro, with ICsp values of 0.65 and 1.0 ug/ml respectively. Interestingly, a mixture of 3-O-benzoylhosloppone and the 5,6-dihydro derivative of this compound exhibited the same ICsp values of 0.65 µg/ml against the above malaria strain as that 'observed for pure 3-O-benzoylhosloppone. Both the root and stem barks of A. carvalhii yielded a known flavone, 5,7-dihydroxy-6,4'-dimethoxyflavone as the major constituent. However, the compound was obtained in a small amount (14.9 mg) which was not enough to carry out antimalarial tests. Brine shrimp bioassay guided isolation of the constituents of the root bark of L. stellatus yielded a hitherto unknown acetylenic fatty acid, together with its methyl ester and a triglyceride derivative. Spectral evidence suggest the acid to be 9-octadecene-llynoic acid. The acid showed a mild antimalarial activity (IC50 = 29 and 30 respectively, against the multidrug resistant K1 and chloroquine sensitive NF54 strains of P. falciparum) while its derivatives were inactive. The bioactive stem bark extracts of this plant, in addition of yielding the acetylenic fatty acid, also afforded two methyl esters of farnesoic acid derivative, viz. methyl 10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate, also known as Juvenile hormone III, and methyl 10,11-dihydroxy-3,7,11-trimethyl-2,6-dodecadienoate. The juvenile hormone III has been found to be mildly active against the K-1 and NF-54 strains of P. falciparum, having IC50 values of 29 and 28 respectively. This compound also showed a mild toxicity in the brine shrimp test (IC50 = 14.26 µg/ml). The pet ether, dichloromethane and ethanol extracts of L. stellatus and A. carvalhii exhibited a mild antimalarial activity against multidrug resistant K1 and chloroquine sensitive NF 54 strains of P. falciparum. The extracts have also been found with mild toxicity in the brine shrimp test with IC50 values of 35 and 16, 48 and 40, and 56 Ng/ml respectively, from the stem and root barks of L. stellatus.