Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

Tiago Rodrigues; Rita C. Guedes; Daniel J.V.A. dos Santos; Marta Carrasco; Jiri Gut; Philip J. Rosenthal; Rui Moreira; Francisca Lopes

doi:10.1016/j.bmcl.2009.05.017

Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

Tiago Rodrigues
, Rita C. Guedes
, Daniel J.V.A. dos Santos
, Marta Carrasco
, Jiri Gut
, Philip J. Rosenthal
, Rui Moreira
, Francisca Lopes

University of Lisbon
University of California at San Francisco

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

27 Citations (Scopus)

Abstract

(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC₅₀ of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Q_o site of cytochrome bc₁.

Original language	English
Pages (from-to)	3476-3480
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2009.05.017
Publication status	Published - 1 Jul 2009
Externally published	Yes

Funding

This work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal); T.R. acknowledges FCT for the Ph.D. grant SFRH/BD/30689/2006. P.J.R. is a Doris Duke Charitable Foundation Distinguished Clinical Scientist.

Funders	Funder number
Fundação para a Ciência e a Tecnologia	SFRH/BD/30689/2006

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

(1H-Pyridin-4-ylidene)amines
Antiplasmodial

Access to Document

10.1016/j.bmcl.2009.05.017

Cite this

@article{4c748221793940fdb5b40be806a91ccb,

title = "Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials",

abstract = "(1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1.",

keywords = "(1H-Pyridin-4-ylidene)amines, Antiplasmodial",

author = "Tiago Rodrigues and Guedes, \{Rita C.\} and \{dos Santos\}, \{Daniel J.V.A.\} and Marta Carrasco and Jiri Gut and Rosenthal, \{Philip J.\} and Rui Moreira and Francisca Lopes",

year = "2009",

month = jul,

day = "1",

doi = "10.1016/j.bmcl.2009.05.017",

language = "English",

volume = "19",

pages = "3476--3480",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "13",

}

TY - JOUR

T1 - Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

AU - Rodrigues, Tiago

AU - Guedes, Rita C.

AU - dos Santos, Daniel J.V.A.

AU - Carrasco, Marta

AU - Gut, Jiri

AU - Rosenthal, Philip J.

AU - Moreira, Rui

AU - Lopes, Francisca

PY - 2009/7/1

Y1 - 2009/7/1

N2 - (1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1.

AB - (1H-Pyridin-4-ylidene)amines containing lipophilic side chains at the imine nitrogen atom were prepared as potential clopidol isosteres in the development of antimalarials. Their antiplasmodial activity was evaluated in vitro against the Plasmodium falciparum W2 (chloroquine-resistant) and FCR3 (atovaquone-resistant) strains. The most active of these derivatives, 4m, had an IC50 of 1 μM against W2 and 3 μM against FCR3. Molecular modeling studies suggest that (1H-pyridin-4-ylidene)amines may bind to the ubiquinol oxidation Qo site of cytochrome bc1.

KW - (1H-Pyridin-4-ylidene)amines

KW - Antiplasmodial

UR - https://www.scopus.com/pages/publications/66349136182

U2 - 10.1016/j.bmcl.2009.05.017

DO - 10.1016/j.bmcl.2009.05.017

M3 - Article

C2 - 19467600

AN - SCOPUS:66349136182

SN - 0960-894X

VL - 19

SP - 3476

EP - 3480

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 13

ER -

Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials

Abstract

Funding

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this