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Novel mannopyranoside esters as sterol 14α-demethylase inhibitors: Synthesis, PASS predication, molecular docking, and pharmacokinetic studies.
Matin, Mohammed M; Chakraborty, Priyanka; Alam, Muhammad S; Islam, Mohammad M; Hanee, Umme.
Afiliação
  • Matin MM; Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chattogram, 4331, Bangladesh. Electronic address: mahbubchem@cu.ac.bd.
  • Chakraborty P; Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chattogram, 4331, Bangladesh.
  • Alam MS; Molecular Modeling & Drug Design Laboratory, Bangladesh Council of Scientific & Industrial Research (BCSIR) Laboratories, Chattogram, 4220, Bangladesh.
  • Islam MM; Department of Biochemistry and Molecular Biology, Faculty of Biological Science, University of Chittagong, Chattogram, 4331, Bangladesh.
  • Hanee U; Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chattogram, 4331, Bangladesh.
Carbohydr Res ; 496: 108130, 2020 Oct.
Article em En | MEDLINE | ID: mdl-32863019
Direct unimolar one-step valeroylation of methyl α-d-mannopyranoside (MDM) furnished mainly 6-O-valeroate. However, similar reaction catalyzed by DMAP resulted 3,6-di-O-valeroate (21%) and 6-O-valeroate (47%) indicating reactivity sequence as 6-OH>3-OH>2-OH,4-OH. To get potential antimicrobial agents, 6-O-valeroate was converted into four 2,3,4-di-O-acyl esters, and 3,6-di-O-valeroate was converted into 2,4-di-O-acetate. Direct tetra-O-valeroylation of MDM gave a mixture of 2,3,4,6-tetra-O-valeroate and 2,3,6-tri-O-valeroate indicating that the C2-OH is more reactive than the equatorial C4-OH. The activity spectra analysis along with in vitro antimicrobial evaluation clearly indicated that these novel MDM esters had better antifungal activities over antibacterial agents. In this connection, molecular docking indicated that these MDM esters acted as competitive inhibitors of sterol 14α-demethylase (CYP51), an essential enzyme for clinical target to cure several infectious diseases. Furthermore, pharmacokinetic studies revealed that these MDM esters may be worth considering as potent candidates for oral and topical administration. Structure activity relationship (SAR) affirmed that saturated valeric chain (C5) in combination with caprylic (C8) chains was more promising CYP51 inhibitor over conventional antifungal antibiotics.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ésteres / Esterol 14-Desmetilase / Inibidores de 14-alfa Desmetilase / Simulação de Acoplamento Molecular / Manose Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ésteres / Esterol 14-Desmetilase / Inibidores de 14-alfa Desmetilase / Simulação de Acoplamento Molecular / Manose Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article