title: Synthesis, in-vitro antibacterial, antifungal, and molecular modeling of potent anti-microbial agents with a combined pyrazole and thiophene pharmacophore.
abstract: Ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate (2) and there derivatives 3a-c, 4, 6a-c and 9a-f were synthesized. The structure of compound 2 was deduced by 1H-NMR, 13C-NMR, FT-IR, MS, microanalysis, and single-crystal X-ray crystallography. The compound crystallized in the monoclinic system, with space group P21/c and cell coordinates a = 8.5752(16) Å, b = 21.046(4) Å, c = 8.2941(12) Å, β = 101.131(6)°, V = 1468.7(4) Å3, and Z = 4. Compounds 2, 3a-c, 4, 5a-c and 9a-f were subjected into in vitro antimicrobial activity tests. Compounds 3a and 3c were more potent than standard drug amphotericin B, showing MIC values of 23.8 ± 0.42 and 24.3 ± 0.68, respectively, against Aspergillus fumigatus while the standard drug MIC was 23.7 ± 0.1. Compound 3c was also more potent (MIC 24.8 ± 0.64) than the standard drug amphotericin B (MIC 19.7 ± 0.2) against Syncephalastrum racemosum. Compounds 4 and 9f also showed promising anti-microbial activity. Molecular modeling was performed for the most active compounds.
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. yahia@ksu.edu.sa.
authors.forename: Yahia Nasser
authors.initials: YN
authors.lastname: Mabkhot
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. nahed.a.k@hotmail.com.
authors.forename: Nahed Ahmed
authors.initials: NA
authors.lastname: Kaal
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. salterary@ksu.edu.sa.
authors.forename: Seham
authors.initials: S
authors.lastname: Alterary
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. salterary@ksu.edu.sa.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al-Showiman
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. ambarakat@ksu.edu.sa.|Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia-21321 Alexandria, Egypt. ambarakat@ksu.edu.sa.
authors.forename: Assem
authors.initials: A
authors.lastname: Barakat
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. ghabbourh@yahoo.com.
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ghabbour
authors.affiliation: Institut für Organische Chemie, Universitat Stuttgart, Pfaffenwaldring 55, Stuttgart 70569, Germany. wolfgang.frey@oc.uni-stuttgart.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Frey
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009090:Mucorales / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002264:Carboxylic Acids; D013876:Thiophenes; C000605222:ethyl 5-acetyl-4-methyl-2-(phenylamino)thiophene-3-carboxylate; D000666:Amphotericin B
keywords: [2+3] cycloaddition; anti-microbial activity; enaminone; molecular modeling; thiophene