2. Academic Validation
  3. Design, synthesis and biological evaluation of some novel sulfonamide derivatives as apoptosis inducers

Design, synthesis and biological evaluation of some novel sulfonamide derivatives as apoptosis inducers

  • Eur J Med Chem. 2017 Jul 28:135:424-433. doi: 10.1016/j.ejmech.2017.04.069.
Khaled O Mohamed 1,  Yassin M Nissan 2,  Afaf A El-Malah 1,  Wafaa A Ahmed 3,  Dina M Ibrahim 4,  Tamer M Sakr 5,  Mohamed A Motaleb 6
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Egypt.
  • 2 Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo 11562, Egypt; Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt. Electronic address: yassin.nissan@hotmail.com.
  • 3 National Cancer Institute, Cancer Biology Department, Cairo University, Egypt.
  • 4 Faculty of Science, Cairo University, Cairo, Egypt.
  • 5 Radioactive Isotopes and Generator Department, Hot Labs Center, Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt. Electronic address: Tamer_sakr78@yahoo.com.
  • 6 Labeled Compounds Department, Hot Labs Center, Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
PMID: 28463785 DOI: 10.1016/j.ejmech.2017.04.069
Abstract

Several novel thiazolidinone and fused thiazolidinone derivatives bearing benzenesulfonamide moiety were synthesized and confirmed via spectral and elemental analyses. The newly synthesized compounds were evaluated for their cytotoxic activity on colorectal Cancer cell line (Caco-2). All the synthesized compounds showed better activity than the Reference Standards (Doxorubicin and 5-FU). Investigation of the apoptotic activity of the most active compounds revealed that compounds 3a, 5a, 5c and 6c activate both Caspase-3 and Fas-ligand in Caco-2 cell line. Compound 3a was the most active compound with Caspase-3 concentration of 0.43 nmol/mL and Fas-ligand concentration of 775.2 pg/mL in treated Caco-2 cells. Compound 3a was radiolabeled with 99mTc and its biodistribution pattern was evaluated in vivo using normal Swiss Albino mice. 99mTc-compound 3a complex didn't exhibit any accumulation in any body organs except for its accumulation in the colon; target organ; where it showed 8.97 ± 1.35 %ID/g at 15min p. i. that elevated till 16.02 ± 2.43 %ID/g at 120min p. i.

Keywords

Apoptosis; Caspase-3; Fas-ligand; Radiolabeling; Technetium-99 m; Thiazolidinone.

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