In silico three dimensional pharmacophore models to aid the discovery and design of new antimalarial agents

Apurba K. Bhattacharjee, Mark G. Kartell, Daniel A. Nichols, Rickey P. Hicks, John E. Van Hamont, Wilbur K. Milhous

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Malaria is one of the most dangerous diseases affecting primarily poor people of tropical and subtropical regions. The search for novel drugs against specific parasites is an important goal for antimalarial drug discovery. This study describes how 3D pharmacophores for antimalarial activity could be developed from known antimalarials and be used as screening tools for virtual compound libraries to identify new antimalarial candidates with examples of indolo[2,1-b]quinazoline-6,12-diones (tryptanthrins) that exhibited in vitro activity below 100 ng/mL. These models mapped on the potent analogues and also onto other well-known antimalarial drugs of different chemical classes including quinolines, chalcones, rhodamine dyes, Pfmrk CDK inhibitors, malarial KASIII inhibitors, and plasmepsin inhibitors. The pharmacophores allowed search and identification of new antimalarials from in-house multi-conformer 3D CIS database and enabled custom designed synthesis of new potent analogues that are found to be potent against in vitro W2, D6, and TM91C235 strains of P. falciparum.

Original languageEnglish (US)
Title of host publicationComputational Science - ICCS 2006
Subtitle of host publication6th International Conference, Proceedings
PublisherSpringer Verlag
Pages387-394
Number of pages8
ISBN (Print)3540343792, 9783540343790
DOIs
StatePublished - Jan 1 2006
EventICCS 2006: 6th International Conference on Computational Science - Reading, United Kingdom
Duration: May 28 2006May 31 2006

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume3991 LNCS - I
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Other

OtherICCS 2006: 6th International Conference on Computational Science
CountryUnited Kingdom
CityReading
Period5/28/065/31/06

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ASJC Scopus subject areas

  • Theoretical Computer Science
  • Computer Science(all)

Cite this

Bhattacharjee, A. K., Kartell, M. G., Nichols, D. A., Hicks, R. P., Van Hamont, J. E., & Milhous, W. K. (2006). In silico three dimensional pharmacophore models to aid the discovery and design of new antimalarial agents. In Computational Science - ICCS 2006: 6th International Conference, Proceedings (pp. 387-394). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 3991 LNCS - I). Springer Verlag. https://doi.org/10.1007/11758501_54