Antiprotozoal Activity of Thymoquinone (2-Isopropyl-5-methyl-1,4-benzoquinone) for the Treatment of Leishmania major-Induced Leishmaniasis: In Silico and In Vitro Studies

Abstract

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.

Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis: A Comprehensive Review

“…Nanotechnology-based medicine delivery systems have significantly improved healthcare and made it feasible to fight illnesses at the molecular level [ 30 ]. Nanoparticles are elegant vehicles for drug-targeted delivery because of their great stability and carrier capacity ( Figure 2 ) [ 31 , 32 ]. In India, which has the greatest estimated number of TB cases, research is being performed to evaluate what role nanotechnology can play in fixing these issues [ 33 ].…”

“…Nanoemulsion-based Drug Delivery Systems: Nanoemulsions have received a lot of attention recently for the study and development of novel drug delivery systems due to their thermodynamic stability, high diffusion and absorption rates, ease of production, and high solubility [ 31 , 32 , 38 ].…”

Effect of Edge Activator Combinations in Transethosomal Formulations for Skin Delivery of Thymoquinone via Langmuir Technique

“…Thymoquinone (TQ), 2-Methyl-5-(propan-2-yl) cyclohexa-2,5-diene-1,4-dione, is the main bioactive component of the volatile oil of Nigella sativa seeds [1]. It has been used in conventional medicine as an antioxidant, antimicrobial, anti-inflammatory, and anticancer agent [2][3][4][5][6].…”

The Effect of Edge Activator Combinations using a Langmuir Technique in Transethosomal Formulations for Skin Delivery of Thymoquinone

“…Thymoquinone (TQ) 2-Methyl-5-(propan-2-yl) cyclohexa-2,5-diene-1,4-dione is the main bioactive component found in the volatile oil of Nigella sativa seeds [1]. It has been used in conventional medicine for centuries as an antioxidant, antimicrobial, anti-inflammatory and anticancer agent [2][3][4][5][6].…”