Leishmaniasis, a Neglected Tropical Parasitic Disease (NTPD), is induced by several Leishmania species and is disseminated through sandfly (Lutzomyia longipalpis) bites. The parasite has developed resistance to currently prescribed antileishmanial drugs, and it has become pertinent to the search for new antileishmanial agents. The current study aimed to investigate the in vitro and in silico antileishmanial activity of two newly sourced actinomycins, X₂ and D, produced by the novel Streptomyces smyrnaeus strain UKAQ_23. The antileishmanial activity conducted on promastigotes and amastigotes of Leishmania major showed actinomycin X₂ having half-maximal effective concentrations (EC₅₀), at 2.10 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and selectivity index (SI) values of 0.048 and 1, respectively, while the actinomycin D exhibited EC₅₀ at 1.90 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and SI values of 0.052 and 1. The molecular docking studies demonstrated squalene synthase as the most favorable antileishmanial target protein for both the actinomycins X₂ and D, while the xanthine phosphoribosyltransferase was the least favorable target protein. The molecular dynamics simulations confirmed that both the actinomycins remained stable in the binding pocket during the simulations. Furthermore, the MMPBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) binding energy calculations established that the actinomycin X₂ is a better binder than the actinomycin D. In conclusion, both actinomycins X₂ and D from Streptomyces smyrnaeus strain UKAQ_23 are promising antileishmanial drug candidates and have strong potential to be used for treating the currently drug-resistant leishmaniasis.

Toxoplasmosis is a globally distributed parasitic protozoan disease, caused by Toxoplasma gondii. The infection can result in more severe symptoms with potentially life-threatening in case of immunocompromised individuals. Sulfadiazine and pyrimethamine are the two drugs used as a part of standard therapy for toxoplasmosis. Researchers have demonstrated the therapeutic effects of medicinal plants for toxoplasmosis, which can be used as an alternative to standard drug therapy with reduced side effects. Traditional herbal plants are used by people to cure a large number of parasitic disorders. This review provides new insights into various medicinal plants that are used traditionally for the treatment of toxoplasmosis and other parasitic infections, which can be useful as an alternative treatment option for Toxoplasma gondii infections.

N-heterocyclic carbene (NHC) precursors (2a–i), their pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-themed palladium N-heterocyclic carbene complexes (3a–i) and palladium N-heterocyclic triphenylphosphines complexes (4a–i) were synthesized and characterized by elemental analysis and ¹H NMR, ¹³C NMR, IR, and LC–MS spectroscopic techniques. The (NHC)Pd(II) complexes 3–4 were tested against MCF7 and MDA-MB-231 cancer cells, Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Candida albicans microorganisms, Leishmania major promastigotes and amastigotes, Toxoplasma gondii parasites, and Vero cells in vitro. The biological assays indicated that all compounds are highly active against cancer cells, with an IC₅₀ < 1.5 µg mL⁻¹. Eight compounds proved antibacterial and antileishmanial activities, while only three compounds had strong antifungal activities against C. albicans. In our conclusion, compounds 3 (b, f, g, and h) and 4b are the most suitable drug candidates for anticancer, antimicrobial, and antiparasitical.

Efficient drugs for the treatment of leishmaniasis, which is classified as a neglected tropical disease, are sought for. This review covers potential drug candidates from natural plant, fungus and algae sources, which were described over the last six years. The identification of these natural antileishmanials often based on the knowledge of traditional medicines. Crucial insights into the activities of these natural remedies againstLeishmaniaparasites and against infections caused by these parasites in laboratory animals or patients are provided and compared with selected former active examples published more than six years ago. In addition, immuno‐modulatory natural antileishmanials and recent developments on combination therapies including natural products and approved antileishmanials are discussed. The described natural products revealed promising data warranting further efforts on the discovery and development of new antileishmanials based on patterns from nature.

Leishmaniasis, a neglected tropical parasitic disease (NTPD), is caused by various Leishmania species. It transmits through the bites of the sandfly. The parasite is evolving resistance to commonly prescribed antileishmanial drugs; thus, there is an urgent need to discover novel antileishmanial drugs to combat drug-resistant leishmaniasis. Thymoquinone (2-isopropyl-5-methyl-1,4-benzoquinone; TQ), a primary pharmacologically active ingredient of Nigella sativa (black seed) essential oil, has been reported to possess significant antiparasitic activity. Therefore, the present study was designed to investigate the in vitro and in silico antileishmanial activity of TQ against various infectious stages of Leishmania major (L. major), i.e., promastigotes and amastigotes, and its cytotoxicity against mice macrophages. In silico molecular dockings of TQ were also performed with multiple selected target proteins of L. major, and the most preferred antileishmanial drug target protein was subjected to in silico molecular dynamics (MD) simulation. The in vitro antileishmanial activity of TQ revealed that the half-maximal effective concentration (EC₅₀), half-maximal cytotoxic concentration (CC₅₀), and selectivity index (SI) values for promastigotes are 2.62 ± 0.12 μM, 29.54 ± 0.07 μM, and 11.27, while for the amastigotes, they are 17.52 ± 0.15 μM, 29.54 ± 0.07 μM, and 1.69, respectively. The molecular docking studies revealed that squalene monooxygenase is the most preferred antileishmanial drug target protein for TQ, whereas triosephosphate isomerase is the least preferred. The MD simulation revealed that TQ remained stable in the binding pocket throughout the simulation. Additionally, the binding energy calculations using Molecular Mechanics Generalized-Born Surface Area (MMGBSA) indicated that TQ is a moderate binder. Thus, the current study shows that TQ is a promising antileishmanial drug candidate that could be used to treat existing drug-resistant leishmaniasis.

Purpose In the present work, a group of nine medicinal plants (Sonchus oleraceus, Echinops spinosissimus, Trichodesma africana, Pergularia tomentosa, Teucrium oliverianum, Blepharis ciliaris, Citrllus colocynthis, Cleome amblyocarpa and Aerva javanica) from eight different families were investigated for their in vitro anti-leishmanial activity against the promastigote and amastigote stages of Leishmania major. L. major is the causative agent of cutaneous leishmaniasis (CL) which is one of the major health problems in Saudi Arabia and neighboring countries such as Iraq and Iran. However, the commonly available commercial therapeutics still come with multiple unwanted side effects in addition to parasite resistance, so medicinal plants have attracted attention due to their affordability and beneficial effects. Methods The selected plants were collected from Al Qassim region in the middle of Saudi Arabia, and then extracts were prepared with methanol using overnight soaking for the whole plants. RPMI 1640 was used to culture L. major to obtain promastigotes and intramacrophage amastigotes, which were used later for evaluation of extract activity in vitro via spectrophotometric and microscopic techniques. The MTT assay was used for cytotoxic evaluation of plant extracts against macrophage cells. Data were expressed in mean +/- SD. Linear regression was used for IC50 and CC50 calculation. T test was used for significant differences at P <= 0.05. Results All the plants revealed anti-leishmanial activity against the L. major amastigote stage with IC50 values less than 91 mu g/mL. The three most potent were T. oliverianum, P. tomentosa and C. amblyocarpa with IC50 values of 7.8, 13.7 and 21.5 mu g/mL, respectively. The L. major promastigote stage was more tolerant, so only T. oliverianum extract showed an IC50 less than 30 (26.6 mu g/mL). P. tomentosa is the most toxic plant with CC50 3.1 mu g/mL followed by T. africana CC50 9.5 mu g/mL, the other plants possess CC50 over 40 mu g/mL. The best SI values were obtained from the C. amblyocarpa and T. oliverianum extracts against the L. major amastigote stages with 5.7 and 5.3, respectively. Conclusion We can conclude that T. oliverianum, P. tomentosa and C. amblyocarpa are the best anti-leishmanial plants, so further phytochemical studies for isolation of active ingredients are highly recommended.