Computational investigation of turmeric phytochemicals targeting PTR1 enzyme of Leishmania species

Wasia Ullah; Wen-Feng Wu; Nosheen Malak; Nasreen Nasreen; Ayman A Swelum; Liliana Aguilar Marcelino; Sadaf Niaz; Adil Khan; Mourad Ben Said; Chien-Chin Chen

doi:10.1016/j.heliyon.2024.e27907

Computational investigation of turmeric phytochemicals targeting PTR1 enzyme of Leishmania species

Heliyon. 2024 Mar 16;10(6):e27907. doi: 10.1016/j.heliyon.2024.e27907. eCollection 2024 Mar 30.

Authors

Wasia Ullah¹, Wen-Feng Wu², Nosheen Malak¹, Nasreen Nasreen¹, Ayman A Swelum³, Liliana Aguilar Marcelino⁴, Sadaf Niaz¹, Adil Khan^{5

6}, Mourad Ben Said^{7

8}, Chien-Chin Chen^{9

10

11

12}

Affiliations

¹ Department of Zoology, Abdul Wali Khan University Mardan, Mardan, 23200, Pakistan.
² Department of Radiology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 600, Taiwan.
³ Department of Animal Production, College of Food and Agriculture Sciences, King Saud University, Riyadh, 1451, Saudi Arabia.
⁴ National Center for Disciplinary Research in Animal Health and Safety (INIFAP), Km 11 Federal Road Cuernavaca-Cuautla, 62550, Jiutepec, Morelos, Mexico.
⁵ Department of Zoology, Bacha Khan University Charsadda, Charsadda, 24420, Pakistan.
⁶ Department of Biology, Mount Allison University, Sackville, E4L 1G7, New Brunswick, Canada.
⁷ Laboratory of Microbiology, National School of Veterinary Medicine of Sidi Thabet, University of Manouba, Manouba, 2010, Tunisia.
⁸ Department of Basic Sciences, Higher Institute of Biotechnology of Sidi Thabet, University of Manouba, Manouba, 2010, Tunisia.
⁹ Department of Biotechnology and Bioindustry Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.
¹⁰ Department of Pathology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 600, Taiwan.
¹¹ Department of Cosmetic Science, Chia Nan University of Pharmacy and Science, Tainan, 717, Taiwan.
¹² Ph.D. Program in Translational Medicine, Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, 40227, Taiwan.

Abstract

In this study, we used in silico techniques to identify available parasite treatments, representing a promising therapeutic avenue. Building upon our computational initiatives aimed at discovering natural inhibitors for various target enzymes from parasites causing neglected tropical diseases (NTDs), we present novel findings on three turmeric-derived phytochemicals as inhibitors of Leishmania pteridine reductase I (PTR1) through in silico methodologies. PTR1, a crucial enzyme in the unique folate metabolism of trypanosomatid parasites, holds established therapeutic significance. Employing MOE software, a molecular docking analysis assesses the efficacy of turmeric phytochemicals against Leishmania PTR1. Validation of the docking protocol is confirmed with an RMSD value of 2. Post-docking, compounds displaying notable interactions with critical residues and binding affinities ranging between -6 and -8 kcal/mol are selected for interaction pattern exploration. Testing twelve turmeric phytochemicals, including curcumin, zingiberene, curcumol, curcumenol, eugenol, bisdemethoxycurcumin, tetrahydrocurcumin, tryethylcurcumin, turmerones, turmerin, demethoxycurcumin, and turmeronols, revealed binding affinities ranging from -5.5 to -8 kcal/mol. Notably, curcumin, demethoxycurcumin, and bisdemethoxycurcumin exhibit binding affinities within -6.5 to -8 kcal/mol and establish substantial interactions with catalytic residues. These phytochemicals hold promise as lead structures for rational drug design targeting Leishmania spp. PTR in future applications. This work underscores the potential of these identified phytochemicals in the development of more effective inhibitors, demonstrating their relevance in addressing neglected tropical diseases caused by parasites.

Keywords: Binding affinities; Enzyme inhibition; In silico techniques; Leishmania pteridine reductase I (PTR1); Molecular docking analysis; Neglected tropical diseases; Parasite treatments; Rational drug design; Therapeutic potential; Turmeric-derived phytochemicals.