Natural products as starting point for the discovery of new bioactive compounds: Drug candidates with antiophidic, anticancer and antiparasitic properties

Abstract

The experience of the Laboratory of Bioorganic Chemistry of the Federal University do Rio de Janeiro (LQB‐UFRJ ®) on the use of abundant natural products such as safrole, eugenol and derivatives, as starting material for the synthesis of new anticancer, antiparasitic and antiophidic drug candidates is briefly described. Twelve derivatives of the naturally occurring coumestan wedelolactone and six derivatives of the naturally occurring pterocarpan edunol were synthesized and evaluated as antiophidic. Two coumestans (LQB‐34, LQB‐ 93) and one pterocarpan (LQB‐100) were more potent and bioselective than the natural products used as reference, being active in vitro (antihaemorragic effect and myoprotection) and in vivo (mice) against different snake venoms. The naturally occurring pterocarpan 4‐hydroxymaackian (LQB‐79) and five derivatives were also prepared and evaluated on leukemia cell lines, including multi drug resistance (MDR) cell lines. The natural product (LQB‐79) was the most potent and bioselective.