In Vitro, In Silico, and Scanning Electron Microscopy Study ofAnti-leishmanial Efficacy of New Synthetic 3-Imidazolyl Flavan Fxime onLeishmania tropica

Introduction: Antimonials have been traditional therapeutic agents for leishmaniasis for decades, but selecting the optimal treatment regimen remains challenging. Alternative systemic treatments, including liposomal amphotericin B and sodium stibogluconate, have shown unclear efficacy in Leishmania tropica cutaneous leishmaniasis. The objective of this study was to evaluate the efficacy of a new synthetic 3-Imidazolyl flavan oxime (IFO) against Leishmania tropica, using in vitro, in silico, and Scanning Electron Microscopy (SEM) analyses. Methods: A standard strain of Leishmania tropica was cultured to assess the in vitro antileishmanial effects of the new synthetic azole. Additionally, scanning electron microscopy was conducted to reveal structural changes in the parasite during treatment. Results: The IC50 value of IFO was 26.5 µg/mL for the promastigote stage, which was significantly lower than that of ketoconazole (KCZ, IC50 = 192 µg/mL) and meglumine antimoniate (MA, IC50 = 234 µg/mL) (P < 0.05). IFO also decreased the Mean Infection Rate (MIR) to 24.78 ± 9.66% and the Mean Number of Amastigotes Per Macrophage (MNAPM) to 1.69 ± 0.31. These values for macrophages treated with KCZ were 37.78 ± 9.18 and 1.91 ± 0.43, with MA 53.33 ± 17.79% and 2.04 ± 0.36, and control 76.67 ± 1.53 and 3.17 ± 0.14, respectively (P = 0.01). Parasite survival (PS) for IFO, KCZ, MA, and control was 53.31 ± 0.26%, 60.25 ± 1.73%, 64.35 ± 1.64%, and 76.67 ± 1.53%, respectively. Inhibition of intracellular amastigote growth (%) for IFO, KCZ, and MA was 46.7%, 35.65%, and 20.38%, respectively. Discussion: Cutaneous leishmaniasis is a significant health problem that has faced treatment challenges, motivating the search for new therapeutic compounds. Azoles have demonstrated considerable anti-leishmanial effects and have attracted attention as potential treatment options. Our synthetic azole exhibited reliable efficacy against L. tropica in both amastigote and promastigote stages, with low toxicity. Conclusion: The results demonstrated notable anti-leishmanial effects of IFO against Leishmania tropica, suggesting it may be considered a potent therapeutic agent. conclusion: The obtained results revealed the notable effects of the compound on the amastigote and promastigote stages of the parasite and can be considered a potent anti-leishmanial agent