Doctoral thesis defense in Organic and Medicinal Chemistry by Mr. Abdelali CHIHAB

Euromed University of Fes (UEMF) is pleased to inform the public of the

doctoral thesis defense in “Organic and medicinal chemistry”

The thesis defense will take place on Tuesday December 10, 2024 at 09:30 at UEMF 

Location: the Main Hall of the Incubator (LOC001994) 

The thesis will be presented by Mr. Abdelali CHIHAB

Under the title:

“Design, synthesis and characterization of novel bioactive molecules and evaluation of their SARS-CoV-2 inhibitory activities.”

 

Abstract 

COVID-19, caused by SARS-CoV-2, has triggered an unprecedented global health crisis, emphasizing the urgent need for developing new antiviral therapies. Among the promising therapeutic targets, the main viral protease (Mpro) plays a crucial role in the maturation of viral polyproteins essential for virus replication. Inhibiting this enzyme represents a key strategy to block the viral life cycle.

This thesis focuses on the development of new bioactive molecules targeting the main enzymes of SARS-CoV-2, particularly Mpro and PLpro, to contribute to the fight against COVID-19. This work combines approaches in organic chemistry, molecular modeling, and ADMET evaluation to design and synthesize derivatives based on ethacrynic acid, indole, and other molecules derived from modified amino acids.

The synthesized compounds were characterized using spectroscopic techniques (NMR, IR, UV, HRMS) and tested for their interactions with the target enzymes. The results revealed promising properties, including favorable binding energies and significant reactivity with key residues, suggesting inhibitory potential. In vivo validation was also considered to confirm the efficacy and safety of the compounds.

This research paves the way for the design of new antiviral agents that could be developed to treat viral infections while advancing knowledge in medicinal chemistry applied to emerging viruses.

Abstract 

COVID-19, caused by SARS-CoV-2, has provoked an unprecedented global health crisis, underlining the urgency of developing new antiviral therapies. Among the promising therapeutic targets, the main viral protease (Mpro) plays a crucial role in the maturation of viral polyproteins necessary for virus replication. Inhibiting this enzyme represents a key strategy to block the virus’s life cycle.

This thesis deals with the development of new bioactive molecules targeting the main enzymes of SARS-CoV-2, notably Mpro and PLpro, to contribute to the fight against COVID-19. This work combines approaches from organic chemistry, molecular modeling, and ADMET evaluation to design and synthesize derivatives based on ethacrynic acid, indole and other molecules derived from modified amino acids.

The compounds studied were characterized using spectroscopic techniques (NMR, IR, UV, HRMS) and tested for their interaction with the target enzymes. The results show promising properties, including favorable binding energies and good reactivity with key residues, suggesting inhibitory potential. An in vivo validation was also considered to confirm the efficacy and safety of the compounds.

This research opens the way to the design of new antivirals that could be developed to treat viral infections, while enriching knowledge on medicinal chemistry applied to emerging viruses.

This thesis will be presented before the jury members:

Last name and First name	Institution	Position
Pr. Fouad OUAZZANI CHAHDI	USMBA	President
Pr. El Mestafa EL HADRAMI	USMBA	Rapporteur
Prof. Abdellatif BOUKIR	USMBA	Rapporteur
Prof. Abdelkrim EL KADIB	UEMF	Rapporteur
Prof. Gérald GUILLAUMET	University of Orléans	Examiner
Pr. Mohamed AKSSIRA	UH2C	Examiner
Prof. Nabil EL BRAHMI	UEMF	Co-supervisor of the Thesis
Prof. Said EL KAZZOULI	UEMF	Thesis Supervisor