Design of hybrid molecules as antimycobacterial compounds: Synthesis of isoniazid-naphthoquinone derivatives and their activity against susceptible and resistant strains of Mycobacterium tuberculosis

Bioorganic & Medicinal Chemistry
Wallace J ReisEufrânio N da Silva Júnior

Abstract

Isoniazid-naphthoquinone hybrids were synthesized and evaluated against a susceptible (H37Rv) strain and two isoniazid-resistant strains (INHR1 and INHR2) of Mycobacterium tuberculosis. The antimycobacterial activity of the derivatives was determined based on the resazurin microtiter assay and their cytotoxicity in adhered mouse monocyte macrophage J774.A1 cells (ATCC TIB-67). Of the twenty-two compounds evaluated against the three strains of M. tuberculosis, twenty-one presented some activity against the H37Rv and INHR1 (katG S315T) or INHR2 (inhA C(-5)T) strains. Compounds 1a, 2a, and 8a were effective against the INHR1 strain, and compounds 1a, 1b, 2a, 3a, 5a, 5b and 8a were effective against the INHR2 strain, with MICs in the range of 3.12-6.25 µg/mL. Compounds 1b and 5b were the most active against H37Rv, with MIC of 0.78 µg/mL. Based on the selectivity index, 1b and 5b can be considered safe as a drug candidate compounds. These results demonstrate that quinoidal compounds can be used as promising scaffolds for the development of new anti-TB drugs and hybrids with activity against M. tuberculosis-susceptible and INH-resistant strains.

References

Aug 1, 1984·Journal of Medicinal Chemistry·K Schaffner-SabbaJ W Wasley
Jun 16, 2001·Antimicrobial Agents and Chemotherapy·I Orme, UNKNOWN Tuberculosis Drug Screening Program
Jul 18, 2002·Antimicrobial Agents and Chemotherapy·Juan-Carlos PalominoFrançoise Portaels
Jun 24, 2003·Bioorganic & Medicinal Chemistry·Ngampong KongkathipPalangpon Kongsaeree
Feb 28, 2006·European Journal of Medicinal Chemistry·Raphael S F SilvaSolange L de Castro
Nov 24, 2007·Annual Review of Microbiology·Catherine Vilchèze, William R Jacobs
Nov 30, 2007·European Journal of Medicinal Chemistry·Eufrânio N da SilvaAntônio V Pinto
Apr 2, 2008·Bioorganic & Medicinal Chemistry·Eufrânio N da Silva JúniorSolange L de Castro
Oct 1, 1948·Journal of the American Chemical Society·L F FIESER, M FIESER
May 16, 2009·Current Medicinal Chemistry·Juan Carlos PalominoPedro Almeida da Silva
Sep 12, 2009·Chemico-biological Interactions·Igal ElingoldMarta Dubin
Dec 2, 2009·Journal of Medicinal Chemistry·Eufrânio N da SilvaAntônio V Pinto
Apr 7, 2010·Bioorganic & Medicinal Chemistry·Benjamin J MulchinBridget L Stocker
Nov 19, 2010·Jornal brasileiro de pneumologia : publicaça̋o oficial da Sociedade Brasileira de Pneumologia e Tisilogia·Marcos Abdo ArbexFernando Augusto Fiúza de Mello
Dec 1, 2010·European Journal of Medicinal Chemistry·Eufrânio N da SilvaAntonio V Pinto
Jun 3, 2011·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·E C Böttger
Aug 13, 2011·Chemical Research in Toxicology·Bruno C CavalcantiCláudia Pessoa
Oct 8, 2013·European Journal of Medicinal Chemistry·Solange L de CastroEufrânio N da Silva Júnior
May 24, 2014·The Journal of Antimicrobial Chemotherapy·Tomasz JagielskiJacek Bielecki
Feb 4, 2015·Chemical Biology & Drug Design·Rangappa S KeriBhari Mallanna Nagaraja
Jul 23, 2015·Tuberculosis·Nicole Fogel
Dec 8, 2015·European Journal of Medicinal Chemistry·Paula F CarneiroVitor F Ferreira
Jul 8, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marcilia P CostaValder N Freire
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Apr 10, 2017·European Journal of Medicinal Chemistry·Yuan-Qiang HuXiang Wu
Nov 9, 2017·Bioorganic & Medicinal Chemistry Letters·Yasodakrishna SajjaLingaiah Nagarapu
Jan 15, 2018·Tuberculosis and Respiratory Diseases·Hyung Woo Kim, Ju Sang Kim
Apr 15, 2018·Biochimica Et Biophysica Acta. Proteins and Proteomics·Johayra SimithyAngela I Calderón
Apr 25, 2018·Frontiers in Microbiology·Priscila C B HalickiDaniela F Ramos
Oct 13, 2018·Chemical Science·Tiago RodriguesGonçalo J L Bernardes
Oct 31, 2018·Chemical Communications : Chem Comm·Gleiston G DiasLutz Ackermann
Nov 18, 2018·Free Radical Biology & Medicine·Ana Cristina S BombaçaRubem F S Menna-Barreto

❮ Previous
Next ❯

Citations

Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Irina ZarafuCristiana Radulescu
Nov 8, 2020·European Journal of Medicinal Chemistry·Qijie GongXiaojin Zhang
Jan 9, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·James M WoodEufrânio N da Silva Júnior
May 2, 2021·Chemical Biology & Drug Design·Priscila Cristina Bartolomeu HalickiDaniela Fernandes Ramos

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antitubercular Agents

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antitubercular Agents (ASM)

Antitubercular agents are pharmacologic agents for treatment of tuberculosis. Discover the latest research on antitubercular agents here.

Antiparasitics

Antiparasitics are medications which are indicated for the treatment of parasitic diseases. Discover the latest research on antiparasitics here.