2. Academic Validation
  3. New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors

New acrylamide-sulfisoxazole conjugates as dihydropteroate synthase inhibitors

  • Bioorg Med Chem. 2020 May 1;28(9):115444. doi: 10.1016/j.bmc.2020.115444.
Tamer Nasr 1,  Samir Bondock 2,  Tamer M Ibrahim 3,  Walid Fayad 4,  Ahmed B Ibrahim 5,  Neveen A AbdelAziz 6,  Tamer M Sakr 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, 11795 Helwan, Cairo, Egypt. Electronic address: [email protected].
  • 2 Department of Chemistry, Faculty of Science, King Khalid University, 9004 Abha, Saudi Arabia; Department of Chemistry, Faculty of Science, Mansoura University, ET-35516 Mansoura, Egypt. Electronic address: [email protected].
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafr El-Sheikh 33516, Egypt.
  • 4 Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza 12622, Egypt.
  • 5 Labeled Compounds Department, Hot Labs Center, Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
  • 6 Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, 12451, Sixth of October City, Giza, Egypt.
  • 7 Radioactive Isotopes and Generators Department, Hot Laboratories Centre, Atomic Energy Authority, P.O. Code 13759 Cairo, Egypt. Electronic address: [email protected].
PMID: 32220521 DOI: 10.1016/j.bmc.2020.115444
Abstract

New functionalized acrylamide derivatives bearing sulfisoxazole moiety were designed to target Bacterial dihydropteroate synthase (DHPS). The in vitro antimicrobial activities of these compounds were assessed. The E-configuration of compound 5b was proved by single crystal X-ray analysis. Compounds 5g and 5h displayed double the activity of ampicillin against B. subtilis. Also, 5h was two times more active than gentamycin against E. coli. Interestingly, compounds 5f-g, 7c, 8a, 8c exhibited two folds the potency of amphotericin B against S. racemosum while 5h displayed three folds the activity of amphotericin B against S. racemosum. Most of the synthesized compounds showed superior activities to the parent sulfisoxazole and were non-toxic to normal cells. DHPS is confirmed to be a putative target for our compounds via antagonizing their Antibacterial activity by the folate precursor (p-aminobenzoic acid) and product (methionine) on E. coli ATCC 25922. Docking experiments against DHPS rationalized the observed Antibacterial activity. Additionally, compound 5g was evaluated as a selective targeting vector for 99mTc that showed a remarkable uptake and targeting ability towards the Infection site that was induced in mice.

Keywords

Acrylamide; Antimicrobial agents; Molecular docking; Radiolabeling; Sulfisoxazole; Thioglycoside.

Figures
Products