دورية أكاديمية
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Design, Synthesis, In Silico and POM Studies for the Identification of the Pharmacophore Sites of Benzylidene Derivatives.

التفاصيل البيبلوغرافية
العنوان: Design, Synthesis, In Silico and POM Studies for the Identification of the Pharmacophore Sites of Benzylidene Derivatives.
المؤلفون: Hosen MI; Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh., Mukhrish YE; Department of Chemistry, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia., Jawhari AH; Department of Chemistry, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia., Celik I; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38280, Turkey., Erol M; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri 38280, Turkey., Abdallah EM; Department of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Saudi Arabia., Al-Ghorbani M; Department of Chemistry, Faculty of Science and Arts, Ulla, Taibah University, Medina 41477, Saudi Arabia., Baashen M; Department of Chemistry, Science and Humanities College, Shaqra University, Ad-Dawadmi 11911, Saudi Arabia., Almalki FA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia., Laaroussi H; Laboratory of Applied Chemistry & Environment, Faculty of Sciences, Mohammed Premier University, Oujda 60000, Morocco., Hadda TB; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.; Laboratory of Applied Chemistry & Environment, Faculty of Sciences, Mohammed Premier University, Oujda 60000, Morocco., Kawsar SMA; Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2023 Mar 13; Vol. 28 (6). Date of Electronic Publication: 2023 Mar 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Antifungal Agents*/chemistry , Anti-Infective Agents*/chemistry, Humans ; Molecular Structure ; Molecular Docking Simulation ; Pharmacophore ; Benzylidene Compounds ; Structure-Activity Relationship ; Anti-Bacterial Agents/chemistry ; Bacteria ; Microbial Sensitivity Tests
مستخلص: Due to the uneven distribution of glycosidase enzyme expression across bacteria and fungi, glycoside derivatives of antimicrobial compounds provide prospective and promising antimicrobial materials. Therefore, herein, we report the synthesis and characterization of six novel methyl 4,6- O -benzylidene-α-d-glucopyranoside (MBG) derivatives ( 2 - 7 ). The structures were ascertained using spectroscopic techniques and elemental analyses. Antimicrobial tests (zone of inhibition, MIC and MBC) were carried out to determine their ability to inhibit the growth of different Gram-positive, Gram-negative bacteria and fungi. The highest antibacterial activity was recorded with compounds 4 , 5 , 6 and 7 . The compounds with the most significant antifungal efficacy were 4 , 5 , 6 and 7 . Based on the prediction of activity spectra for substances (PASS), compounds 4 and 7 have promising antimicrobial capacity. Molecular docking studies focused on fungal and bacterial proteins where derivatives 3 and 6 exhibited strong binding affinities. The molecular dynamics study revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger remained stable, both over time and in physiological conditions. Structure-activity relationships, including in vitro and in silico results, revealed that the acyl chains [lauroyl-(CH 3 (CH 2 ) 10 CO-), cinnamoyl-(C 6 H 5 CH=CHCO-)], in combination with sugar, were found to have the most potential against human and fungal pathogens. Synthetic, antimicrobial and pharmacokinetic studies revealed that MBG derivatives have good potential for antimicrobial activity, developing a therapeutic target for bacteria and fungi. Furthermore, the Petra/Osiris/Molinspiration (POM) study clearly indicated the presence of an important (O1 δ- ----O2 δ- ) antifungal pharmacophore site. This site can also be explored as a potential antiviral moiety.
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معلومات مُعتمدة: 2022-2023 University of Chittagong
فهرسة مساهمة: Keywords: PASS prediction; POM theory; antimicrobial; identification of pharmacophore sites; methyl 4,6-O-benzylidene-α-d-glucopyranoside; molecular dynamics
المشرفين على المادة: 0 (Antifungal Agents)
0 (Benzylidene Compounds)
0 (Anti-Infective Agents)
0 (Anti-Bacterial Agents)
تواريخ الأحداث: Date Created: 20230329 Date Completed: 20230330 Latest Revision: 20230331
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10053039
DOI: 10.3390/molecules28062613
PMID: 36985587
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules28062613