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Development of novel isatin-nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing-bacteria.
Elsayed, Zainab M; Eldehna, Wagdy M; Abdel-Aziz, Marwa M; El Hassab, Mahmoud A; Elkaeed, Eslam B; Al-Warhi, Tarfah; Abdel-Aziz, Hatem A; Abou-Seri, Sahar M; Mohammed, Eman R.
Afiliação
  • Elsayed ZM; Faculty of Pharmacy, Scientific Research and Innovation Support Unit, Kafrelsheikh University, Kafrelsheikh, Egypt.
  • Eldehna WM; Faculty of Pharmacy, Scientific Research and Innovation Support Unit, Kafrelsheikh University, Kafrelsheikh, Egypt.
  • Abdel-Aziz MM; Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Kafrelsheikh University, Kafrelsheikh, Egypt.
  • El Hassab MA; The Regional Center for Mycology & Biotechnology, Al-Azhar University, Cairo, Egypt.
  • Elkaeed EB; Department of Pharmaceutical Chemistry, School of Pharmacy, Badr University in Cairo, Badr City, Egypt.
  • Al-Warhi T; Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Ad Diriyah, Saudi Arabia.
  • Abdel-Aziz HA; Faculty of Pharmacy (Boys), Department of Pharmaceutical Organic Chemistry, Al-Azhar University, Cairo, Egypt.
  • Abou-Seri SM; Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
  • Mohammed ER; Department of Applied Organic Chemistry, National Research Center, Giza, Egypt.
J Enzyme Inhib Med Chem ; 36(1): 384-393, 2021 Dec.
Article em En | MEDLINE | ID: mdl-33406941
Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a-m and 9a-c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 µg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 µg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49-7.81 µg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.
Assuntos
Oxirredutases do Álcool/antagonistas & inibidores; Antibacterianos/síntese química; Proteínas de Bactérias/antagonistas & inibidores; Farmacorresistência Bacteriana/efeitos dos fármacos; Hidrazinas/química; Isatina/química; Mycobacterium tuberculosis/enzimologia; Oxirredutases do Álcool/química; Oxirredutases do Álcool/metabolismo; Antibacterianos/farmacologia; Proteínas de Bactérias/química; Proteínas de Bactérias/metabolismo; Sítios de Ligação; Bordetella pertussis/química; Bordetella pertussis/enzimologia; Bordetella pertussis/isolamento & purificação; Bronquite/tratamento farmacológico; Bronquite/microbiologia; Desenho de Fármacos; Farmacorresistência Bacteriana/genética; Haemophilus influenzae/química; Haemophilus influenzae/enzimologia; Haemophilus influenzae/isolamento & purificação; Isoniazida/farmacologia; Klebsiella pneumoniae/química; Klebsiella pneumoniae/enzimologia; Klebsiella pneumoniae/isolamento & purificação; Testes de Sensibilidade Microbiana; Simulação de Acoplamento Molecular; Moraxella catarrhalis/química; Moraxella catarrhalis/enzimologia; Moraxella catarrhalis/isolamento & purificação; Mycobacterium tuberculosis/química; Mycobacterium tuberculosis/isolamento & purificação; Ligação Proteica; Conformação Proteica; Domínios e Motivos de Interação entre Proteínas; Streptococcus pneumoniae/química; Streptococcus pneumoniae/enzimologia; Streptococcus pneumoniae/isolamento & purificação; Estreptomicina/farmacologia; Relação Estrutura-Atividade; Tuberculose/tratamento farmacológico; Tuberculose/microbiologia
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Farmacorresistência Bacteriana / Oxirredutases do Álcool / Hidrazinas / Isatina / Antibacterianos / Mycobacterium tuberculosis Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Farmacorresistência Bacteriana / Oxirredutases do Álcool / Hidrazinas / Isatina / Antibacterianos / Mycobacterium tuberculosis Idioma: En Ano de publicação: 2021 Tipo de documento: Article