The recent proliferation and prevalence of antimicrobial multi-resistant infections has prompted the development of other strategies and alternatives to urgently combat this global threat. Rifampicin-resistant Mycobacterium tuberculosis was included in the Critical Priority class of pathogens defined by the World Health Organization, due to the global impact on public health, the severity of the disease on affected patients and the increasing incidence of multi-drug-resistant strains [1-2].

In this context, past mastering of remedies formulation appears as a wealth of resources for present research. In particular, Arab Medieval Pharmacopeias (AMP) were explored by our interdisciplinary team gathering researchers from biology, chemistry, humanities and informatics sciences [3] with the aim to discover new bioactive compounds from ancient preparations to combat actual health threats.

Modern approaches were conducted together for the selection a remedy from AMP, the targeting of potential antimicrobial compounds and their isolation. Three manuscripts from the 9th to the 12th Century were used to create an interactive database in order to bring out relevant anti-tuberculosis remedies [4]. A formulation assembling plants resins, roots and metals was highlighted. After sourcing, extraction and in vitro evaluation against Mycobacterium tuberculosis H37Rv, five resins extracts showed anti-Mycobacterium activity (MIC values from 100 to 400 µg/mL). The study was then focus on Bdellium, a gum-resin from Commiphora wightii (Burseraceae) based on its selective action against M. tuberculosis strain. The targeted isolation of putatively bioactive compounds was guided by the combination of HPLC-HRMS/MS data dereplication and molecular networking, both with pharmacophoric deconvolution which is differential analyses of 2D NMR data linked to bioactivity. Pharmacophoric deconvolution indicates that diterpenes structural pattern could be responsible of the anti-Mycobacterium tuberculosis activity. Their targeted isolation and antimicrobial evaluation are ongoing to confirm our analytical and historical approaches.

[1] Ordonez., et al., Sci. Transl. Med., 2019, 11, 508. [2] Pakamwong et al., J. Chem. Inf. Model., 2024, 64, 5991−6002. [3] Abdallah et al., J. Trace Elem. Med. Biol., 2022, 71, 126926. [4] El Haff et al., Front. Artif. Intell., 2024, 392, 2354-2361.