Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos.
N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10-12 h. One hundred percent mortality was observed at concentrations≥50 µM. At sub-lethal concentrations (10-30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%-40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules.
Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. fmuhammad@ksu.edu.sa.
Muhammad
M
Farooq
Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. nabutaha@ksu.edu.sa.
Nael Abu
NA
Taha
Department of Chemistry, the University of Texas at Austin, Austin, TX 78712, USA. rrbutorac@utexas.edu.
Rachel R
RR
Butorac
Department of Chemistry, the University of Texas at Austin, Austin, TX 78712, USA. daevans@utexas.edu.
Daniel Anthony
DA
Evans
Materials Science and Technology Program, College of Arts and Sciences, Qatar University, PO Box 2713, Doha, Qatar. aelzatahry@qu.edu.qa.
Ahmed A
AA
Elzatahry
Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. eaelsayed@ksu.edu.sa.|Natural and Microbial Products Department, National Research Centre, Dokki, Cairo 12311, Egypt. eaelsayed@ksu.edu.sa.
Elsayed Ahmed
EA
Elsayed
Bioproducts Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. wadaan@ksu.edu.sa.
Mohammad A M
MA
Wadaan
Petrochemical Research Chair, Department of Chemistry, King Saud University, Riyadh 11451, Saudi Arabia. ssdeyab@ksu.edu.sa.
Salem S
SS
Al-Deyab
Department of Chemistry, the University of Texas at Austin, Austin, TX 78712, USA. acowley@cm.utexas.edu.
Alan H
AH
Cowley
D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology
D006571:Heterocyclic Compounds; C030011:carbene; D006046:Gold; D008697:Methane
BIAN; N-heterocyclic carbenes complexes; neurotoxicity; oxidative stress; zebrafish