Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates

Apurba K. Bhattacharjee; Mark G. Hartell; Daniel A. Nichols; Rickey P. Hicks; Benjamin Stanton; John E. Van Hamont; Wilbur K. Milhous

doi:10.1016/j.ejmech.2003.10.004

Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates

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

Research output: Contribution to journal › Article › peer-review

136 Scopus citations

Abstract

A widely applicable three-dimensional QSAR pharmacophore model for antimalarial activity was developed from a set of 17 substituted antimalarial indolo[2,1-b]quinazoline-6,12-diones (tryptanthrins) that exhibited remarkable in vitro activity (below 100 ng/mL) against sensitive and multidrug-resistant Plasmodium falciparum malaria. The pharmacophore, which contains two hydrogen bond acceptors (lipid) and two hydrophobic (aromatic) features, was found to map well onto many well-known antimalarial drug classes including quinolines, chalcones, rhodamine dyes, Pfmrk cyclin dependent kinase inhibitors, malarial FabH inhibitors, and plasmepsin inhibitors. The phamacophore allowed searches for new antimalarial candidates from multiconformer 3D databases and enabled custom designed synthesis of new potent analogues.

Original language	English (US)
Pages (from-to)	59-67
Number of pages	9
Journal	European Journal of Medicinal Chemistry
Volume	39
Issue number	1
DOIs	https://doi.org/10.1016/j.ejmech.2003.10.004
State	Published - Jan 2004
Externally published	Yes

Keywords

Malaria
Pharmacophore
QSAR

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2003.10.004

Cite this

Bhattacharjee, A. K., Hartell, M. G., Nichols, D. A., Hicks, R. P., Stanton, B., Van Hamont, J. E., & Milhous, W. K. (2004). Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates. European Journal of Medicinal Chemistry, 39(1), 59-67. https://doi.org/10.1016/j.ejmech.2003.10.004

Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates. / Bhattacharjee, Apurba K.; Hartell, Mark G.; Nichols, Daniel A. et al.
In: European Journal of Medicinal Chemistry, Vol. 39, No. 1, 01.2004, p. 59-67.

Research output: Contribution to journal › Article › peer-review

Bhattacharjee, AK, Hartell, MG, Nichols, DA, Hicks, RP, Stanton, B, Van Hamont, JE & Milhous, WK 2004, 'Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates', European Journal of Medicinal Chemistry, vol. 39, no. 1, pp. 59-67. https://doi.org/10.1016/j.ejmech.2003.10.004

Bhattacharjee AK, Hartell MG, Nichols DA, Hicks RP, Stanton B, Van Hamont JE et al. Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates. European Journal of Medicinal Chemistry. 2004 Jan;39(1):59-67. doi: 10.1016/j.ejmech.2003.10.004

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Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three dimensional pharmacophore modeling and identification of new antimalarial candidates

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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