Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

Meir Touitou; Fabrizio Manetti; Camila Maringolo Ribeiro; Fernando Rogerio Pavan; Nicolò Scalacci; Katarina Zrebna; Neelu Begum; Dorothy Semenya; Antima Gupta; Sanjib Bhakta; Timothy D. Mchugh; Hanoch Senderowitz; Melina Kyriazi; Daniele Castagnolo

doi:https://doi.org/10.1021/acsmedchemlett.9b00515

Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

Meir Touitou, Fabrizio Manetti, Camila Maringolo Ribeiro, Fernando Rogerio Pavan, Nicolò Scalacci, Katarina Zrebna, Neelu Begum, Dorothy Semenya, Antima Gupta, Sanjib Bhakta, Timothy D. Mchugh, Hanoch Senderowitz, Melina Kyriazi, Daniele Castagnolo

Bar-Ilan University

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

Abstract

A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.

Original language	English
Pages (from-to)	638-644
Number of pages	7
Journal	ACS Medicinal Chemistry Letters
Volume	11
Issue number	5
DOIs	https://doi.org/10.1021/acsmedchemlett.9b00515
State	Published - 14 May 2020

Keywords

Tuberculosis
antimycobacterial drug
drug resistance
intracellular tuberculosis
pyrroles

All Science Journal Classification (ASJC) codes

Drug Discovery
Biochemistry
Organic Chemistry

UN SDGs

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

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https://doi.org/10.1021/acsmedchemlett.9b00515

Cite this

Touitou, M., Manetti, F., Ribeiro, C. M., Pavan, F. R., Scalacci, N., Zrebna, K., Begum, N., Semenya, D., Gupta, A., Bhakta, S., Mchugh, T. D., Senderowitz, H., Kyriazi, M., & Castagnolo, D. (2020). Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria. ACS Medicinal Chemistry Letters, 11(5), 638-644. https://doi.org/10.1021/acsmedchemlett.9b00515

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title = "Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria",

abstract = "A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.",

keywords = "Tuberculosis, antimycobacterial drug, drug resistance, intracellular tuberculosis, pyrroles",

author = "Meir Touitou and Fabrizio Manetti and Ribeiro, {Camila Maringolo} and Pavan, {Fernando Rogerio} and Nicol{\`o} Scalacci and Katarina Zrebna and Neelu Begum and Dorothy Semenya and Antima Gupta and Sanjib Bhakta and Mchugh, {Timothy D.} and Hanoch Senderowitz and Melina Kyriazi and Daniele Castagnolo",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 American Chemical Society.",

year = "2020",

month = may,

day = "14",

doi = "https://doi.org/10.1021/acsmedchemlett.9b00515",

language = "الإنجليزيّة",

volume = "11",

pages = "638--644",

journal = "ACS Medicinal Chemistry Letters",

issn = "1948-5875",

publisher = "American Chemical Society",

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Touitou, M, Manetti, F, Ribeiro, CM, Pavan, FR, Scalacci, N, Zrebna, K, Begum, N, Semenya, D, Gupta, A, Bhakta, S, Mchugh, TD, Senderowitz, H, Kyriazi, M & Castagnolo, D 2020, 'Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria', ACS Medicinal Chemistry Letters, vol. 11, no. 5, pp. 638-644. https://doi.org/10.1021/acsmedchemlett.9b00515

TY - JOUR

T1 - Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

AU - Touitou, Meir

AU - Manetti, Fabrizio

AU - Ribeiro, Camila Maringolo

AU - Pavan, Fernando Rogerio

AU - Scalacci, Nicolò

AU - Zrebna, Katarina

AU - Begum, Neelu

AU - Semenya, Dorothy

AU - Gupta, Antima

AU - Bhakta, Sanjib

AU - Mchugh, Timothy D.

AU - Senderowitz, Hanoch

AU - Kyriazi, Melina

AU - Castagnolo, Daniele

PY - 2020/5/14

Y1 - 2020/5/14

N2 - A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.

AB - A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.

KW - Tuberculosis

KW - antimycobacterial drug

KW - drug resistance

KW - intracellular tuberculosis

KW - pyrroles

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U2 - https://doi.org/10.1021/acsmedchemlett.9b00515

DO - https://doi.org/10.1021/acsmedchemlett.9b00515

M3 - مقالة

C2 - 32435364

SN - 1948-5875

VL - 11

SP - 638

EP - 644

JO - ACS Medicinal Chemistry Letters

JF - ACS Medicinal Chemistry Letters

IS - 5

ER -

Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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