Biological activity of halimane derivatives through diversity-oriented synthesis

In recent times, the emergence of antibiotic-resistant bacteria and chemotherapeutic resistance has prompted the quest for bioactive compounds to develop new and more effective drugs. Plectranthus spp. (Lamiaceae) are known for their traditional medicinal properties, being a rich source of natural lead molecules with diverse structures and biological activities. P. ornatus Codd. has been used traditionally in Africa, Asia and Brazil for alleviating a wide range of ailments, including digestive tract (stomach and liver), diuretic, pain, fever, inflammation and infections. The halimane compound 11R*-acetoxyhalima-5,13E-dien- 15-oic acid (HAL), the main constituent of P. ornatus’ acetonic extract, revealed interesting biological activities, such as moderate anti-inflammatory effects, antimycobacterial and cytotoxicity. A previous study from our group, yielded promising results regarding the antimycobacterial activity of a HAL derivative, which inhibited bacterial growth almost to the same extent as a clinically used antitubercular drug. Based on this, the aim of the present work was to fully physiochemically characterize the HAL starting material for potential pharmaceutical use. HAL was characterized through SCXRD, FTIR, HSM (170°C), DSC and TG. SCXRD results showed that HAL presents orthorhombic symmetry, crystallizing in the space group P212121, and that its carboxylic groups can form hydrogen bonds with the binding motif R_2^2 (8). Also, new HAL derivatives were prepared, functionalized using amines, with improved biological activity. HAL derivatives 1, 2 and 3 ([Fig. 1]) were successfully synthesized and their structural characterization confirmed by ¹H-, ¹³C- NMR and FTIR. Further physiochemical biological activity characterization of the analogues is on-going.

Fig. 1 Structure of HAL and synthesized derivatives 1, 2 and 3

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Artikel online veröffentlicht:
16. November 2023