title: Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds.
abstract: RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Helwan 11829, Egypt. Electronic address: hany.s.ibrahim@gmail.com.
authors.forename: Hany S
authors.initials: HS
authors.lastname: Ibrahim
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Helwan 11829, Egypt.
authors.forename: Wagdy M
authors.initials: WM
authors.lastname: Eldehna
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt. Electronic address: hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.affiliation: The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Elaasser
authors.affiliation: The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Abdel-Aziz
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D010793:Phthalazines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D010793:Phthalazines; D013455:Sulfur; C043388:phthalazine
keywords: Antibacterial agents; Phthalazin-1(2H)-4-one; RAB1; Sulfa drugs