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Yahya Mouhamad Salma

Associate professor
Chemistry - Biochemistry department - Section III - Tripoli
Speciality: Biochemistry
Specific Speciality: BioChimie Cancerologie

Teaching 8 Taught Courses
(2014-2015) Bioc 417 - Biochemical Technology and Engineering

M1 Biochemistry

(2014-2015) Bioc 437 - Cell Culture and Types

M1 Biochemistry

(2014-2015) CHTH 580 - Training

M Refining and hydrocarbon technology

(2014-2015) Chim 219 - The Chemistry of daily life

BS Chemistry

(2014-2015) Chim 271 - General Chemistry

BS Physics

(2014-2015) Chim 271 - General Chemistry

BS Physics

(2014-2015) Chim 280 - General chemistry and organic chemistry Lab

BS Earth and life sciences

(2014-2015) Bioc 350 - Food Biochemistry Lab

BS Biochemistry

Publications 6 publications
Y. Salma, S. Ballereau, S. Ladeira, C. Lepetit, R. Chauvin, N. Andrieu-Abadie and Y. Génisson, Single- and double-chained truncated jaspine B analogues: asymmetric synthesis, biological evaluation and theoretical study of an unexpected 5-endo-dig process. Tetrahedron 67 (2011) 4253–4262 2011

An optimized synthesis of jaspine B analogues bearing an n-octyl or a p-fluorophenethyl lipophilic appendage was developed. Key to the approach was the use of acetylenic nucleophiles for the stereocontrolled introduction of the side chain and the implementation of a novel cyclization procedure to build the tetrahydrofuran ring. Three N-substituted amine or amide derivatives were also accessed. The biological activity of these four jaspine B analogues was shown to strongly depend on the nature of both the N-substituent and the aliphatic moiety connected to the tetrahydrofuran ring. Gratifyingly, the truncated jaspine B derivative proved to be a pro-apoptotic inhibitor of the conversion of ceramide into sphingomyelin. Finally, the efficient formation of a fused bis-furan derivative according to a 5-endo-dig process was observed under saponification conditions. On the basis of a theoretical study, a mechanistic pathway was delineated highlighting the Lewis acidity of the K+ ion as the driving force for this transformation in a strongly alkaline medium.

Yahya Salma, Stéphanie Ballereau, Carine Maaliki, Sonia Ladeira, Nathalie Andrieu-Abadie and Yves Génisson Flexible and enantioselective access to jaspine B and biologically active chain-modified analogues thereof Organic & Biomolecular Chemistry Issue 14, 2010 2010

Whereas the all-cis tetrahydrofuran framework of the cytotoxic anhydrophytosphingosine jaspine B is considered as a relevant pharmacophore, little is known about the influence of the aliphatic chain of this amphiphilic molecule on its activity. We developed a synthetic strategy allowing flexible introduction of various lipophilic fragments in the jaspine's skeleton. The route was validated with two distinct approaches to jaspine B. Five chain-modified analogues were also prepared. Biological evaluation of these derivatives demonstrated a good correlation between their cytotoxicity and their capacity to inhibit conversion of ceramide into sphingomyelin in melanoma cells. A series of potent and selective inhibitors of sphingomyelin production was thus identified. Furthermore, the good overall potency of an omega-aminated analogue allowed us to dissociate of the pharmacological action of jaspine B from its amphiphilic nature.

Salma Y, Lafont E, Therville N, Carpentier S, Bonnafé MJ, Levade T, Génisson Y, Andrieu-Abadie N. The natural marine anhydrophytosphingosine, Jaspine B, induces apoptosis in melanoma cells by interfering with ceramide metabolism. Biochemical Pharmacology. 2009, 78, 477-485. 2009

Marine environment has frequently afforded a variety of biologically active compounds with strong anticancer and cytotoxic properties. In the present study, the mechanism of action of Jaspine B, an anhydrophytosphingosine derivative isolated from the marine sponge Jaspis sp., was investigated. Jaspine B was able to dose- and time-dependently decrease the viability of murine B16 and human SK-Mel28 melanoma cells. On these cells, Jaspine B treatment triggered cell death by typical apoptosis as illustrated by phosphatidylserine externalization, the release of cytochrome c and caspase processing. These effects were associated with increased intracellular ceramide levels owing to perturbed ceramide metabolism. Indeed, Jaspine B exposure strongly inhibited the activity of sphingomyelin synthase (SMS), an enzyme that converts de novo ceramide into the membrane lipid sphingomyelin. Moreover, whereas Jaspine B-induced cell death was enhanced in SMS1-depleted cells, it was strongly inhibited in cells that stably overexpress human SMS1. Finally, the cytotoxic effects of Jaspine B truncated analogs were also shown to be dependent on SMS activity. Altogether, Jaspine B is able to kill melanoma cells by acting on SMS activity and consequently on ceramide formation, and may represent a new class of cytotoxic compounds with potential applications in anticancer melanoma therapy.

F. Sabourdy, B. Kedjouar, SC. Sorli, S. Colié, D. Milhas, Y. Salma and T. Levade, Functions of sphingolipid metabolism in mammals--lessons from genetic defects. Biochimica et Biophysica Acta. 2008, 4, 145-83. 2008

Much is known about the pathways that control the biosynthesis, transport and degradation of sphingolipids. During the last two decades, considerable progress has been made regarding the roles this complex group of lipids play in maintaining membrane integrity and modulating responses to numerous signals. Further novel insights have been provided by the analysis of newly discovered genetic diseases in humans as well as in animal models harboring mutations in the genes whose products control sphingolipid metabolism and action. Through the description of the phenotypic consequences of genetic defects resulting in the loss of activity of the many proteins that synthesize, transport, bind, or degrade sphingolipids, this review summarizes the (patho)physiological functions of these lipids.

Yves Génisson, Lydia Lamandé, Yahya Salma, Nathalie Andrieu-Abadie, Chantal André, Michel Baltas Enantioselective access to a versatile 4-oxazolidinonecarbaldehyde and application to the synthesis of a cytotoxic jaspine B truncated analogue. Tetrahedron Asymmetry. 2007, 18, 857-864. 2007

The preparation of the versatile aldehyde 15 via a concise route based on a formal anti-asymmetric aminohydroxylation and its use in a 5-step synthesis of a cytotoxic C12 analogue of the natural anhydrophytosphingosine jaspine B is presented.

Vanessa Faugeroux, Yves Génisson, Yahya Salma, Patricia Constant, Michel Baltas Synthesis and biological evaluation of conformationally constrained analogues of the antitubercular agent ethambutol. Bioorganic & Medicinal Chemistry. 2007, 17, 5866-76. 2007

Three (S)-prolinol-derived conformationally restricted analogues of the antitubercular agent ethambutol were prepared and tested against Mycobacterium tuberculosis.

Languages
Arabic

Native or bilingual proficiency

English

Professional working proficiency

French

Full professional proficiency