Catharanthus Alkaloids XIII: Antineoplastic and Hypotensive Activity of Alkaloid Fractions and Certain Alkaloids From Catharanthus lanceus

Abstract

Hypotensive evaluation of 14 alkaloid fractions derived from C. lanceus roots and leaves in anesthetized, normotensive rats and dogs revealed that eight of the fractions reduced blood pressure from 22–73 per cent for periods ranging from 38 to more than 378 min., at doses of 8–40 mg./Kg. Yohimbine, a potent α-adrenergic blocking agent, was isolated from three of the eight active fractions. However, removal of the yohimbine from one of these fractions did not result in a loss of hypotensive activity, thus indicating that other hypotensive agents may be present. Leurosine, perivine, and pericyclivine elicited only transient hypotensive activity, whereas vindoline, tetrahydroalstonine, ajmalicine, lochnerinine, and periformyline failed to induce a hypotensive response at several dose levels. The same crude alkaloid fractions were evaluated for antineoplastic activity against the P-1534 leukemia with only one of the 14 fractions being active against this neoplasm. Leurosine, isolated from the active fraction, was shown to be a potent antineoplastic alkaloid with a high degree of cytotoxicity. Lochnerinine, although devoid of activity against the P-1534 leukemia, exhibited reproducible cytotoxicity against the 9 KB cell culture. Vindoline, catharanthine, desacetylvindoline, perivine, perivinol, periformyline, pericyclivine, pericalline, catharine, ajmalicine, tetrahydroalstonine, and yohimbine were devoid of P-1534 leukemia activity, as well as cytotoxicity. Monitoring of column chromatographic cuts of the active fraction with the P-1534 leukemia has shown that at least one additional alkaloid, active against this neoplasm, is present.