Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents

Simon M. Jones; Jonathan E.  Urch; Reto Brun; John L. Harwood; Colin Berry; Ian H.  Gilbert

doi:10.1016/j.bmc.2003.11.023

Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents

Simon M. Jones, Jonathan E. Urch, Reto Brun, John L. Harwood, Colin Berry, Ian H. Gilbert

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

80 Citations (Scopus)

Abstract

A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	683-692
Number of pages	10
Journal	Bioorganic & Medicinal Chemistry
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.bmc.2003.11.023
Publication status	Published - 15 Feb 2004

UN SDGs

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

Access to Document

10.1016/j.bmc.2003.11.023

Cite this

@article{66d8de418c224eb98fc615ce030e8503,

title = "Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents",

abstract = "A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.",

author = "Jones, {Simon M.} and Urch, {Jonathan E.} and Reto Brun and Harwood, {John L.} and Colin Berry and Gilbert, {Ian H.}",

year = "2004",

month = feb,

day = "15",

doi = "10.1016/j.bmc.2003.11.023",

language = "English",

volume = "12",

pages = "683--692",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents

AU - Jones, Simon M.

AU - Urch, Jonathan E.

AU - Brun, Reto

AU - Harwood, John L.

AU - Berry, Colin

AU - Gilbert, Ian H.

PY - 2004/2/15

Y1 - 2004/2/15

N2 - A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.

AB - A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.

U2 - 10.1016/j.bmc.2003.11.023

DO - 10.1016/j.bmc.2003.11.023

M3 - Article

C2 - 14759729

SN - 0968-0896

VL - 12

SP - 683

EP - 692

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 4

ER -

Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this