PROGNOSES OF ANTIMALARIAL EFFECTIVENESS FROM STUDIES OF RELATIONSHIPS BETWEEN MOLECULAR CONSTITUTION AND CHEMOTHERAPEUTIC RESPONSE.
Abstract
The purpose of the research was to chemotherapeutically eradicate malarias in the human host; drug resistant strains of P. falciparum constitute the primary target. Our aim is to suggest molecules for synthesis and testing which have a high probability of success as effective antimalarials. The approach to the problem includes (1) the virtually complete physicochemical characterization of analogous series of molecules of interest as known or potential antimalarials, (2) molecular orbital calculations of these molecules, and (3) the building of quantitative structure-activity models. Results for this report period include the successful prediction of the cholinesterase inhibitory potency of 1-decyl-3-(N-ethyl-N-methylcarbamoyl)piperidine hydrobromide and a comparative study of the Hansch and Free-Wilson models. Several variations of the Hansch equations were applied to selected naphthoquinone antimalarial data reported by Fieser et al. in 1948. No one mathematical model which adequately describes the entire group of antimalarials was found. A discussion on 'quantitative structure-activity relationships and molecular orbitals in medicinal chemistry,' and 'physicochemical parameters in drug design,' appear in the appendices.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1969
- Accession Number
- AD0693872
Entities
People
- William P. Purcell
Organizations
- University of Tennessee