Abstract:

Pharmacological activity and drugability are two essential components for drug discovery. Natural products are a rich source of therapeutic drugs. Compared to synthetic molecules, natural products offer greater structural diversity and complexity. Although naturally occurring substances usually are good lead compounds, they seldom meet the demands for drugability. It is necessary to modify and optimize these structural phenotypes to increase potency and selectivity, improve physico-chemical, biochemical and pharmacokinetic properties, eliminate or reduce side effects, and attain intellectual properties.

A potential anti-cancer compound Camptothecin (CPT) isolated from Camptotheca acuminate induces cell death by DNA damage, but this compound exhibited low aqueous solubility and severe toxicity. Synthetic CPT analogues including topotecan, irinotecan, (CPT-11), 9-amino camptothecin (9-AC), lurtotecan and rubitecan, were found to effectively inhibit DNA topoisomerase-I, a critical enzyme in DNA replication and transcription.

Keeping this in view, the structural modification of a few natural lead molecules are presented and the pharmacological activities of the secondary lead compounds reported.

Date:     Friday, 10 May 2013

Time:    11:30 - 12:30

Venue: The Mendeleev (2.32) – Chemistry Building

CONTACT PERSON: Dr LA Pilcher (012) 420 5384       [email protected]