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Medicinal chemistry in Djibouti

Medicinal chemistry in Djibouti

Through chemical hemisynthesis, TWAS-Sida research grant awardee Ahmed Saïd Mohamed of Djibouti works to enhance the therapeutic properties of molecules extracted from indigenous plants

Located in the Horn of Africa, bordered by Ethiopia, Somalia, Eritrea, in front of the Gulf of Aden and the Red Sea, Djibouti is the third-smallest country in mainland Africa. With a very dry climate and hot temperatures, which may reach 45º C, Djibouti is a biodiversity hotspot, hosting more than 1,500 animal species and 800 plant varieties.

Here, where science and scientific research are steadily growing, works Mohamed, an outstanding chemist now with the Institute for Medicinal Research, Center for Research and Study, Djibouti (Centre d'Étude et de Recherche de Djibouti), who received a TWAS-Sida research grant that pushed forward his research on how to enhance the activity of natural substances with therapeutic properties.

"The TWAS-Sida research grant was a booster to my career," acknowledged Mohamed, who earned his PhD in chemistry in 2016 from the University of Franche-Comté in Besançon, France, before heading back to Djibouti. "With the grant, I was able to develop my original idea and initiate a new research topic within the Institute for Medicinal Research." Mohamed is the first-ever TWAS grantee from Djibouti.

Mohamed chose the scientific career, and chemistry in particular, by passion, because he was fascinated by the way molecules combine and react mutually. Initially, he focused on organic and organometallic chemistry as a tool to learn how to synthesize molecules of interest. Soon, however, he turned to structural modification of natural substances, to merge the two fields.

"Djibouti is rich in plant varieties, many of which belong to the traditional health-care system of this country," he observed. "However, for many of them, very few scientific studies have been carried out: we know that they have (or might have) some therapeutic properties, but for many of them more detailed studies would be useful, to implement their curative activity."

This consideration led Mohamed to develop an interest in natural substances, to improve their biological activities, with an eye to the local traditional medicine. 'Medicinal chemistry', as this field of investigation is called, aims to integrate indigenous knowledge with modern scientific methods.

Moving from the plant to the bioactive molecule, however, requires a great effort: one must locate or cultivate the plant, wait for its maturity, collect the flowers or the fruits. Then the harvest must reach a laboratory, where scientists proceed with the extraction. The latter step is quite lengthy and frequently involved very high costs, the scientist explained.

"I started preliminary studies to assess the feasibility of carrying out the hemisynthesis of natural substances, which is a new focus of research at the Institute for Medicinal Research. It consists in the synthesis of substances that already exist in nature, and in their subsequent structural modification, to improve their biological activity," he clarified.

The isolation of small quantities of natural substances from a rare plant, or from plants difficult to access, makes the synthesis often indispensable, Mohamed added. Synthetic substances are also produced faster and in greater quantity, and are identical to those existing in nature, with exactly the same properties.

Traditional medicine of Djibouti uses a number of plants for medicinal purposes, and Mohamed, with some colleagues, concentrated on some of them, obtaining vegetal extracts with molecules that then they further modify for therapeutic purposes.

At the time of writing, he was working, for example, on extracts from Avicennia marina, commonly known as grey or white mangrove, a species that likes high-salt soils and that has antioxidant and antifungal characteristics. Avicennia marina is one of the four species growing in Djibouti, the other three have not been fully studied. "I will continue to investigate the three other species. I believe that they should all be valued for their medicinal properties," Mohamed.

In another research, the scientist synthesized organometallic compounds with anticancer effect in the treatment of breast and prostate cancer. These compounds will be further evaluated in 'in vitro' tests, to confirm that they can be considered for 'in vivo' preliminary tests.

Mohamed and his colleagues were able to find positive sides also to the COVID-19 pandemic. The need to fight the viral infection spurred new investigations that gave promising outcomes: "We chose three medicinal plants of Djibouti—Acacia seyal, Cymbopogon commutatus and Indigofera caerulea—whose anti-SARS-Cov 2 effectiveness was previously evaluated through in silico tests. And we found that they do have inhibitory activity towards SARS-Cov 2 infections. Subsequently, we could also improve the activity of these substances by modifying their basic structure," explained Mohamed.

"The development of the synthesis and the hemisynthesis of natural substances is very useful in the medicinal and pharmaceutical fields, and allows the scaling-up of interesting molecules, with lower costs than those of the extraction procedure," he concluded.

Mohamed's short-term plans are aligned with his early successful results: as the starter of medicinal chemistry in Djibouti, he hopes to create a competitive research group with strong competencies and international visibility.

Cristina Serra