Six (G1-G6) novel organogallium complexes of the general formula [Ga(R)quin] (where R = Et, Pr, Bu, Bu, Bu and hexyl; quin = quinolin-8-olate, CHNO) have been synthesised and fully characterised. Single crystal X-ray diffraction shows the complexes adopt a five-coordinate geometry through dimerisation. Complexes G1-G5 were analytically pure and could undergo further biological analysis. [Ga(hex)quin] G6 could not be satisfactorily purified and was excluded from biological assays. H NMR spectroscopy indicated the complexes are stable to hydrolysis over 24 hours in 'wet' d-DMSO. Complexes G1-G5 were assessed for their anti-leishmanial activity towards three separate strains: , and , with varied results toward the promastigote form. G1 and G2 were found to be the most selective with little to no toxicity towards mammalian cell lines. Amastigote invasion assays on the three strains showed that [Ga(Bu)quin] G3 and [Ga(Bu)quin] G4 gave the best all round anti-parasitic activity with percentage infection ranges of 1.50-3.00% and 3.25-7.50% respectively, with G3 out-performing the drug control amphotericin B in all three assays. The activity was found to correlate with lipophilicity and water solubility, with the most effective G3 proving the most lipophilic and least water soluble.
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Int J Parasitol Drugs Drug Resist
December 2024
São Paulo State University (Unesp), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil. Electronic address:
Leishmaniasis is a neglected disease that remains with a limited number of drugs available for chemotherapy and has an increased drug resistance that affects treatment outcomes. Metal-based drugs such as cyclopalladated complex [Pd(dmba)(μ-N)] (CP2), a Leishmania topoisomerase IB inhibitor involved in calcium dysregulation and mitochondrial dysfunction of the parasite, had been an alternative to outline the appearance of chemoresistance. To identify new molecular targets and point out possible resistance mechanisms, a CP2-resistant Leishmania amazonensis (LaR) was selected by stepwise exposure to increasing drug pressure until a line capable of growth in 13.
View Article and Find Full Text PDFIn Silico Pharmacol
December 2024
Laboratory of Cell and Molecular Biology, Department of Botany, Centre of Advanced Study, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, 700019 India.
Visceral Leishmaniasis, caused by is the second most deadly parasitic disease, causing over 65,000 deaths annually. Synthetic drugs available in the market, to combat this disease, have numerous side effects. In this backdrop, we aim to find safer antileishmanial alternatives with minimal side effects from mushrooms, which harbour various secondary metabolites with promising efficacy.
View Article and Find Full Text PDF3 Biotech
January 2025
Cell and Molecular Biology Laboratory, Department of Zoology, Soban Singh Jeena University, Campus Almora, Almora, Uttarakhand India.
Unlabelled: Visceral leishmaniasis (VL), caused by , remains challenging to treat due to severe side effects and increasing drug resistance associated with current chemotherapies. Our study investigates the anti-leishmanial potential of from Uttarakhand, India, with extracts prepared from leaves and stems using ethanol and hexane. Advanced GC-MS analysis identified over 100 bioactive compounds, which were screened using molecular docking to assess their binding to LdHEL-67, a DDX3-DEAD box RNA helicase of donovani.
View Article and Find Full Text PDFAMB Express
December 2024
Department of Parasitology and Mycology, School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran.
Leishmaniasis is a vector-borne disease and one of the most significant neglected tropical diseases. Current anti-leishmanial treatments are often ineffective over extended periods and are associated with toxic side effects, highlighting the urgent need for new, effective, and safe alternative treatments for this infectious disease. The objective of this study was to evaluate the anti-leishmanial effects of a hydroalcoholic extract of Hypericum scabrum (H.
View Article and Find Full Text PDFMol Divers
December 2024
Deparment of Microbiology, Assam University, Silchar, 788011, Assam, India.
Leishmaniasis, a neglected tropical disease caused by various Leishmania species, poses a significant global health challenge, especially in resource-limited regions. Visceral Leishmaniasis (VL) stands out among its severe manifestations, and current drug therapies have limitations, necessitating the exploration of new, cost-effective treatments. This study utilized a comprehensive computational workflow, integrating traditional 2D-QSAR, q-RASAR, and molecular docking to identify novel anti-leishmanial compounds, with a focus on Glycyl-tRNA Synthetase (LdGlyRS) as a promising drug target.
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