Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c

Kawaljit Singh; Malkeet Kumar; Elumalai Pavadai; Krupa Naran; Digby F. Warner; Peter G. Ruminski; Kelly Chibale

doi:10.1016/j.bmcl.2014.05.022

Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c

Kawaljit Singh, Malkeet Kumar, Elumalai Pavadai, Krupa Naran, Digby F. Warner, Peter G. Ruminski, Kelly Chibale

Section of Stem Cell Biology

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

26 Scopus citations

Abstract

New verapamil analogues were synthesized and their inhibitory activities against Mycobacterium tuberculosis H37Rv determined in vitro alone and in combination with rifampicin (RIF). Some analogues showed comparable activity to verapamil and exhibited better synergies with RIF. Molecular docking studies of the binding sites of Rv1258c, a M. tuberculosis efflux protein previously implicated in intrinsic resistance to RIF, suggested a potential rationale for the superior synergistic interactions observed with some analogues.

Original language	English
Pages (from-to)	2985-2990
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2014.05.022
State	Published - Jul 15 2014

Keywords

Efflux pump
Rifampicin
Rv1258c
Tuberculosis
Verapamil

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10.1016/j.bmcl.2014.05.022

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Singh, K., Kumar, M., Pavadai, E., Naran, K., Warner, D. F., Ruminski, P. G., & Chibale, K. (2014). Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c. Bioorganic and Medicinal Chemistry Letters, 24(14), 2985-2990. https://doi.org/10.1016/j.bmcl.2014.05.022

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title = "Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c",

abstract = "New verapamil analogues were synthesized and their inhibitory activities against Mycobacterium tuberculosis H37Rv determined in vitro alone and in combination with rifampicin (RIF). Some analogues showed comparable activity to verapamil and exhibited better synergies with RIF. Molecular docking studies of the binding sites of Rv1258c, a M. tuberculosis efflux protein previously implicated in intrinsic resistance to RIF, suggested a potential rationale for the superior synergistic interactions observed with some analogues.",

keywords = "Efflux pump, Rifampicin, Rv1258c, Tuberculosis, Verapamil",

author = "Kawaljit Singh and Malkeet Kumar and Elumalai Pavadai and Krupa Naran and Warner, {Digby F.} and Ruminski, {Peter G.} and Kelly Chibale",

note = "Funding Information: The University of Cape Town, South African Medical Research Council , and South African Research Chairs initiative of the Department of Science and Technology administered through the South African National Research Foundation are gratefully acknowledged for support (K.C.). ",

year = "2014",

month = jul,

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doi = "10.1016/j.bmcl.2014.05.022",

language = "English",

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Singh, K, Kumar, M, Pavadai, E, Naran, K, Warner, DF, Ruminski, PG & Chibale, K 2014, 'Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c', Bioorganic and Medicinal Chemistry Letters, vol. 24, no. 14, pp. 2985-2990. https://doi.org/10.1016/j.bmcl.2014.05.022

Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c. / Singh, Kawaljit; Kumar, Malkeet; Pavadai, Elumalai et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 14, 15.07.2014, p. 2985-2990.

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

TY - JOUR

T1 - Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c

AU - Singh, Kawaljit

AU - Kumar, Malkeet

AU - Pavadai, Elumalai

AU - Naran, Krupa

AU - Warner, Digby F.

AU - Ruminski, Peter G.

AU - Chibale, Kelly

N1 - Funding Information: The University of Cape Town, South African Medical Research Council , and South African Research Chairs initiative of the Department of Science and Technology administered through the South African National Research Foundation are gratefully acknowledged for support (K.C.).

PY - 2014/7/15

Y1 - 2014/7/15

N2 - New verapamil analogues were synthesized and their inhibitory activities against Mycobacterium tuberculosis H37Rv determined in vitro alone and in combination with rifampicin (RIF). Some analogues showed comparable activity to verapamil and exhibited better synergies with RIF. Molecular docking studies of the binding sites of Rv1258c, a M. tuberculosis efflux protein previously implicated in intrinsic resistance to RIF, suggested a potential rationale for the superior synergistic interactions observed with some analogues.

AB - New verapamil analogues were synthesized and their inhibitory activities against Mycobacterium tuberculosis H37Rv determined in vitro alone and in combination with rifampicin (RIF). Some analogues showed comparable activity to verapamil and exhibited better synergies with RIF. Molecular docking studies of the binding sites of Rv1258c, a M. tuberculosis efflux protein previously implicated in intrinsic resistance to RIF, suggested a potential rationale for the superior synergistic interactions observed with some analogues.

KW - Efflux pump

KW - Rifampicin

KW - Rv1258c

KW - Tuberculosis

KW - Verapamil

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DO - 10.1016/j.bmcl.2014.05.022

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SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Singh K, Kumar M, Pavadai E, Naran K, Warner DF, Ruminski PG et al. Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c. Bioorganic and Medicinal Chemistry Letters. 2014 Jul 15;24(14):2985-2990. doi: 10.1016/j.bmcl.2014.05.022

Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c

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