Cutaneous Leishmaniasis (CL) is a neglected tropical disease, classified by the World Health Organization (WHO) as one of the most unrestrained diseases. The Syrian war and the significant displacement of refugees aggravated the spread of this ailment into several neighboring countries in the Eastern Mediterranean Region (EMR). In Syria, Leishmania tropica is identified as one of the most aggressive and endemic identified species, causing localized or generalized lesions, often chronic or relapsing. Pentavalent antimonial drugs are currently used as first line treatment against CL. Nonetheless, these drugs exhibit several limitations, including the repetitive painful injections, high cost, poor availability, and mainly systemic toxicity. Besides, the emergence of acquired parasitic resistance hinders their potency, stressing the need for new therapies to combat CL. Natural products (NPs) epitomize a valuable source in drug discovery. NPs are secondary metabolites (SMs) produced by plants, sponges, or a wide variety of organisms, including environmental microorganisms. The EMR is characterized by its immense biodiversity, yet it remains a relatively untapped area in drug discovery. NPs of the region were explored over the last 2 decades, but their discoveries lack biogeographical diversity and are limited to the Red Sea. Here, we isolated previously uncultured environmental soil-dwelling Streptomyces sp. HAS1, from Hasbaya region in southeast Lebanon. When fermented in one of our production media named INA, HAS1 produced a crude extract with significant potency against a clinical Leishmania tropica isolate. Using bio-guided fractionation, the bioactive compound was purified and the structure was elucidated by NMR and LC-HRMS. Our findings establish NPs as strong candidates for treating Leishmania tropica and further dwells on the importance of these natural sources to combat microbial infections.

Objective/Background Natural products (NPs) derived from microorganisms are the basis of a plethora of clinically utilized medications, namely, antimicrobial remedies. Although these secondary metabolites have been extensively explored all over the planet, they remain understudied in the Middle East and North Africa (MENA) region. Methods A literature search was conducted to first find NPs that were isolated from environmental fungi and bacteria that inhabit the soils and seawater of the MENA region. Then, purified molecules with biological activity against pathogenic bacteria, biofilms, fungi, and parasites were described in terms of structure, function, and location. Moreover, the methods that could be used to ameliorate the discovery of novel NPs from this region were investigated. Results A multitude of antimicrobial molecules from various chemical classes were found to be derived from the environmental microbes of MENA. Although many were rediscovered, some represented novel structural scaffolds for novel families of antimicrobial agents. Additionally, the geographical distribution showed a high number of these NPs were unraveled in a restricted area leaving much of MENA untapped. Furthermore, as relatively traditional and low-efficiency methods were typically used in the discovery process, advanced high-throughput techniques were suggested to enhance this practice at the regional level. Conclusion MENA represents a fairly unexploited region where antimicrobial drug discovery could be performed comprehensively through the concomitant exploration of untouched geographical locations and advanced molecular techniques.