N2-substituted triazoles as trypanothione reductase inhibitors: in silico evaluation, synthesis, and anti-leishmanial activity

Abraham P, Lamba N, Acosta M, Gholmie J, Dawood HY, Vestal M, Huang K, Hulou M, Asgarzadeh M, Zaidi H, Mekary RA, Smith TR (2017) Antibacterial prophylaxis for gram-positive and gram-negative infections in cranial surgery: A meta-analysis. In Journal of Clinical Neuroscience (Vol. 45, pp. 24–32). Churchill Livingstone. https://doi.org/10.1016/j.jocn.2017.07.039

Al-Humaidi JY, Shaaban MM, Rezki N, Aouad MR, Zakaria M, Jaremko M, Hagar M, Elwakil BH (2022) 1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants. Life 12(9). https://doi.org/10.3390/life12091341

Andreeva OV, Garifullin BF, Zarubaev VV, Slita AV, Yesaulkova IL, Saifina LF, Shulaeva MM, Belenok MG, Semenov VE, Kataev VE (2021) Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity. Mol Diversity 25(1):473–490. https://doi.org/10.1007/s11030-020-10141-y

Article  CAS  Google Scholar 

Ashwini N, Garg M, Mohan CD, Fuchs JE, Rangappa S, Anusha S, Swaroop TR, Rakesh KS, Kanojia D, Madan V, Bender A, Koeffler HP, Basappa, Rangappa KS (2015) Synthesis of 1,2-benzisoxazole tethered 1,2,3-triazoles that exhibit anticancer activity in acute myeloid leukemia cell lines by inhibiting histone deacetylases, and inducing p21 and tubulin acetylation. Bioorg Med Chem 23(18):6157–6165. https://doi.org/10.1016/j.bmc.2015.07.069

Article  CAS  PubMed  Google Scholar 

Bachrach U, Abu-Elheiga L, Schnur LF (1983) Leishmania tropica major: Effect of Paromomycin and Pentamidine on Polyamine Levels in the Skin of Normal and Infected Mice’. Exp Parasitol (55)

Bailey S, SMITH K, FAIRLAMB, A. H., HUNTER WN (1993) Substrate interactions between trypanothione reductase and N 1 -glutathionylspermidine disulphide at 0.28‐nm resolution. Eur J Biochem 213(1):67–75. https://doi.org/10.1111/j.1432-1033.1993.tb17734.x

Article  CAS  PubMed  Google Scholar 

Baiocco P, Colotti G, Franceschini S, Ilari A (2009) Molecular Basis of Antimony Treatment in Leishmaniasis. J Med Chem 52(8):2603–2612. https://doi.org/10.1021/jm900185q

Article  CAS  PubMed  Google Scholar 

Baiocco P, Poce G, Alfonso S, Cocozza M, Porretta GC, Colotti G, Biava M, Moraca F, Botta M, Yardley V, Fiorillo A, Lantella A, Malatesta F, Ilari A (2013) Inhibition of Leishmania infantum Trypanothione Reductase by Azole-Based Compounds: a Comparative Analysis with Its Physiological Substrate by X‐ray Crystallography. ChemMedChem 8(7):1175–1183. https://doi.org/10.1002/cmdc.201300176

Article  CAS  PubMed  Google Scholar 

Battista T, Colotti G, Ilari A, Fiorillo A (2020) Targeting Trypanothione Reductase, a Key Enzyme in the Redox Trypanosomatid Metabolism, to Develop New Drugs against Leishmaniasis and Trypanosomiases. Molecules 25(8):1924. https://doi.org/10.3390/molecules250819

Article  CAS  PubMed  PubMed Central  Google Scholar 

Besson A, Dowdy SF, Roberts JM (2008) CDK inhibitors: cell cycle regulators and beyond. Dev Cell 14(2):159–169

Article  CAS  PubMed  Google Scholar 

Bistrović A, Krstulović L, Stolić I, Drenjančević D, Talapko J, Taylor MC, Kelly JM, Bajić M, Raić-Malić S (2018) Synthesis, anti-bacterial and anti-protozoal activities of amidinobenzimidazole derivatives and their interactions with DNA and RNA. J Enzyme Inhib Med Chem 33(1):1323–1334. https://doi.org/10.1080/14756366.2018.1484733

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brata Das B, Ganguly A, Majumder KH (2008) DNA Topoisomerases of Leishmania: The Potential Targets for Anti-Leishmanial Therapy. Adv Exp Med Biology, 625, 103115

Google Scholar 

Caraballo RH, Pociecha J, Reyes G, Espeche A, Galichio S, Fasulo L, Semprino M (2020) Rufinamide as add-on therapy in children with epileptic encephalopathies other than Lennox–Gastaut syndrome: A study of 34 patients. Epilepsy Behav 108. https://doi.org/10.1016/j.yebeh.2020.107074

Das T, Jayasudha R, Chakravarthy SK, Prashanthi GS, Bhargava A, Tyagi M, Rani PK, Pappuru RR, Sharma S, Shivaji S (2021) Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy. Sci Rep 11(1):2738. https://doi.org/10.1038/s41598-021-82538-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Souza W, Rodrigues JCF (2009) Sterol Biosynthesis Pathway as Target for Anti-trypanosomatid Drugs. Interdisciplinary Perspectives on Infectious Diseases, 2009, 1–19. https://doi.org/10.1155/2009/642502

Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27(5):305–318

Article  CAS  PubMed  Google Scholar 

Lucht F, Fauche A, Allaert FA (1996) Cefatrizine (8 d) versus penicillin v (10 d) for streptococcal pharyngitis in children. Med Mal Infect 26:557–561

Article  Google Scholar 

Egan WJ, Merz KM, Baldwin JJ (2000) Prediction of drug absorption using multivariate statistics. J Med Chem 43(21):3867–3877. https://doi.org/10.1021/jm000292e

Article  CAS  PubMed  Google Scholar 

Gellis A, Dumètre A, Lanzada G, Hutter S, Ollivier E, Vanelle P, Azas N (2012) Preparation and antiprotozoal evaluation of promising β-carboline alkaloids. Biomed Pharmacotherapy 66(5):339–347. https://doi.org/10.1016/j.biopha.2011.12.006

Article  CAS  Google Scholar 

Ghose AK, Viswanadhan VN, Wendoloski JJ (1999) A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1(1):55–68. https://doi.org/10.1021/cc9800071

Article  CAS  PubMed  Google Scholar 

Grymel M, Pastuch-Gawołek G, Lalik A, Zawojak M, Boczek S, Krawczyk M, Erfurt K (2020) Glycoconjugation of Betulin Derivatives Using Copper-Catalyzed 1,3-Dipolar Azido-Alkyne Cycloaddition Reaction and a Preliminary Assay of Cytotoxicity of the Obtained Compounds. Molecules 25(24):6019. https://doi.org/10.3390/MOLECULES25246019

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gupta O, Pradhan T, Bhatia R, Monga V (2021) Recent advancements in anti-leishmanial research: Synthetic strategies and structural activity relationships. Eur J Med Chem 223. https://doi.org/10.1016/j.ejmech.2021.113606. Elsevier Masson s.r.l

Jain V, Jain K (2018) Molecular targets and pathways for the treatment of visceral FIGleishmaniasis. Drug Discovery Today, vol 23. Elsevier Ltd, pp 161–170. 1 https://doi.org/10.1016/j.drudis.2017.09.006

Kalinin DV, Jana SK, Pfafenrot M, Chakrabarti A, Melesina J, Shaik TB, Lancelot J, Pierce RJ, Sippl W, Romier C, Jung M, Holl R (2020) Structure-Based Design, Synthesis, and Biological Evaluation of Triazole-Based smHDAC8 Inhibitors. ChemMedChem 15(7):571–584. https://doi.org/10.1002/cmdc.201900583

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lipinski CA, Dominy BW, Feeney PJ (1997) drug delivery reviews Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. In Adv Drug Deliv Rev (23)

Mahender T, Pankaj W, Kumar SP, Ankur V, Kumar SS (2022) Some scaffolds as anti-leishmanial agents: A review. Mini Rev Med Chem 22(5):743–757

Article  CAS  PubMed  Google Scholar 

Majoor A, Michel G, Marty P, Boyer L, Pomares C (2025) Leishmaniases: Strategies in treatment development. In Parasite (Vol. 32). EDP Sciences. https://doi.org/10.1051/parasite/2025009

Manda S, Khan SI, Jain SK, Mohammed S, Tekwani BL, Khan IA, Vishwakarma RA, Bharate SB (2014) Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines. Bioorg Med Chem Lett 24(15):3247–3250. https://doi.org/10.1016/j.bmcl.2014.06.030

Article  CAS  PubMed  Google Scholar 

McBride A, Walker SL (2018) Diagnostic approach to tropical skin infections. Medicine (United Kingdom), vol 46. Elsevier Ltd, pp 10–15. 1 https://doi.org/10.1016/j.mpmed.2017.10.008

Mohapatra S (2014) Drug resistance in leishmaniasis: Newer developments. Trop Parasitol 4(1):4. https://doi.org/10.4103/2229-5070.129142

Article  PubMed  PubMed Central  Google Scholar 

Nare B, Hardy LW, Beverley SM (1997) The roles of pteridine reductase 1 and dihydrofolate reductase- thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major. J Biol Chem 272(21):13883–13891. https://doi.org/10.1074/jbc.272.21.13883

Article  CAS  PubMed  Google Scholar 

Nguyen C, Kasinathan G, Leal-Cortijo I, Musso-Buendia A, Kaiser M, Brun R, Ruiz-Pérez LM, Johansson NG, González-Pacanowska D, Gilbert IH (2005) Deoxyuridine triphosphate nucleotidohydrolase as a potential antiparasitic drug target. J Med Chem 48(19):5942–5954. https://doi.org/10.1021/jm050111e

Article  CAS  PubMed  Google Scholar 

Padmanabhan PK, Mukherjee A, Singh S, Chattopadhyaya S, Gowri VS, Myler PJ, Srinivasan N, Madhubala R (2005) Glyoxalase I from Leishmania donovani: A potential target for anti-parasite drug. Biochem Biophys Res Commun 337(4):1237–1248. https://doi.org/10.1016/j.bbrc.2005.09.179

Article  CAS  PubMed  Google Scholar 

Patpi SR, Pulipati L, Yogeeswari P, Sriram D, Jain N, Sridhar B, Murthy R, Devi A, Kalivendi T, S. V., Kantevari S (2012) Design, synthesis, and structure-activity correlations of novel dibenzo[b,d furan, dibenzo[b,d]thiophene, and N-methylcarbazole clubbed 1,2,3-triazoles as potent inhibitors of mycobacterium tuberculosis. J Med Chem 55(8):3911–3922. https://doi.org/10.1021/jm300125e

Article  CAS  PubMed  Google Scholar 

Porta EOJ, Ballari MS, Carlucci R, Wilkinson S, Ma G, Tekwani BL, Labadie GR (2023) Systematic study of 1, 2, 3-triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases. Eur J Med Chem 254:115378

Article  CAS  PubMed 

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