Natural lead is a chemical compound derived from living organism. Nature
provides a vast set of structurally diverse compounds that can be used as a medicine.
Traditional knowledge of natural medicine will remain as an important source of future
medicine and therapeutics. A lead compound in drug discovery possesses some
therapeutic applicability, but it may require a series of structural changes to serve as a
drug. The chemical structure of the lead molecule is used as a starting point for
chemical modifications in order to improve its selectivity, potency, pharmacodynamics
and pharmacokinetic parameters. The high-throughput screening (HTS) techniques are
used to screen thousands of compounds to identify potential drug candidates for a given
drug target. The structure-activity relationship (SAR) and absorption, distribution,
metabolisms, excretion and toxicity (ADMET) parameters and other related druglikeness
properties of a lead can be optimized to discover a potential drug. ADMET
assays measure and define the properties such as the rate of metabolism, non-specific
and plasma-protein binding, permeability, liver and kidney toxicity, LogP and
solubility. Furthermore, the process of lead optimization improves the poor druglikeness
of the lead and a new candidate drug can be recommended for in vitro or
clinical testing.
Keywords: ADMET, Drug, Drug Designing, Lead Compound, Medicinal,
Natural, Optimization.