Molecular docking and simulation analysis of selected herbal compounds against GP63, FPPS, and NMT, three important Leishmania major proteins

Seyed Mahmoud Mousavi , Negar Balmeh, Najaf Allahyari Fard, Zahra Ghayour Najafabadi, Sedighe Saberi, Hajar Shabandoust, Parisa Mousavi, Shima Gharibi, Mustafa Ghanadian , Hossein Hejazi

Abstract


Background and purpose: Leishmaniasis has been categorized as one of the most significant tropical illnesses, often ignored. This study aimed to find effective plant compounds to combat the pathogenicity of the Leishmania parasite.

Experimental approach: The 3D structures of the zinc leishmanolysin glycoprotein 63 (GP63), farnesyl diphosphate synthase (FPPS), and N-myristoyltransferase (NMT) proteins from L. major, as well as blockers and 4000 herbal compounds, were retrieved from the PubChem database. A molecular docking study was performed on Leishmania proteins using PyRx software. The activity, ADMET characteristics, and daily carcinogenicity were taken from “Swiss ADME”, “way 2 drug”, and “Lazar” websites. Molecules with the greatest docking scores for each protein were chosen for molecular dynamics simulation using GROMACS.

Findings/Results: Molecular docking experiments revealed that withaperuvin D and lagerstannin A have a strong affinity for the GP63 protein. Moreover, strictinin showed the highest binding affinity for FPPS, whereas the top compounds for NMT were chelidimerine, friedelin, and hypericin. Additionally, luteolin 3'-o-glucuronide, protohypericin, and amentoflavone had high binding affinity for all three proteins, and amentoflavone had the highest binding energy of all the proteins. Based on RMSD, RMSF, Rg, PCA, MM/PBSA binding energy, and SASA, the molecular dynamic simulation results indicated relatively stable interactions between these ligands and the mentioned proteins during the simulation period.

Conclusion and implications: Given the pharmaceutical information, the mentioned substances may have anti-inflammatory and wound-healing properties in addition to blocking proteins. Therefore, experimentally examining these compounds in the future can help control and treat leishmaniasis.

 

 


Keywords


FPPS; GP63; Herbal compounds; Leishmaniasis; Molecular dynamics; NMT.

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References


Olivier M, Hassani K. Protease inhibitors as prophylaxis against leishmaniasis: new hope from the major surface protease gp63. Future Med Chem. 2010;2(4):539-542.DOI: 10.4155/fmc.10.17.

Sheikhmoradi V, Saberi S, Saghaei L, Pestehchian N, Fassihi A. Synthesis and antileishmanial activity of antimony (V) complexes of hydroxypyranone and hydroxypyridinone ligands. Res Pharm Sci. 2018;13(2):111-120.DOI: 10.4103/1735-5362.223793.

Rahnama V, Motazedian MH, Mohammadi-Samani S, Asgari Q, Ghasemiyeh P, Khazaei M. Artemether-loaded nanostructured lipid carriers: preparation, characterization, and evaluation of in vitro effect on Leishmania major. Res Pharm Sci. 2021;16(6):623-633.DOI: 10.4103/1735-5362.327508.

Joshi PB, Kelly BL, Kamhawi S, Sacks DL, McMaster WR. Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol. 2002;120(1): 33-40.DOI: 10.1016/s0166-6851(01)00432-7.

Bowyer PW, Gunaratne RS, Grainger M, Withers-Martinez C, Wickramsinghe SR, Tate EW, et al. Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum. Biochem J. 2007;408(2):173-180.DOI: 10.1042/bj20070692.

Rogers MJ, Mönkkönen J, Munoz MA. Molecular mechanisms of action of bisphosphonates and new insights into their effects outside the skeleton. Bone. 2020;139:115493,1-39.DOI: 10.1016/j.bone.2020.115493.

Mukherjee S, Basu S, Zhang K. Farnesyl pyrophosphate synthase is essential for the promastigote and amastigote stages in Leishmania major. Mol Biochem Parasitol. 2019;230:8-15.DOI: 10.1016/j.molbiopara.2019.03.001.

Sanders JM, Song Y, Chan JMW, Zhang Y, Jennings S, Kosztowski T, et al. Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption. J Med Chem. 2005;48(8):2957-2963.DOI: 10.1021/jm040209d.

Brannigan JA, Roberts SM, Bell AS, Hutton JA, Hodgkinson MR, Tate EW, et al. Diverse modes of binding in structures of Leishmania major N-myristoyltransferase with selective inhibitors. IUCrJ. 2014;1(4):250-260.DOI: 10.1107/S2052252514013001.

Frearson JA, Brand S, McElroy SP, Cleghorn LA, Smid O, Stojanovski L, et al. N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature. 2010;464(7289):728-732.DOI: 10.1038/nature08893.

Kim JH, Didi-Cohen S, Khozin-Goldberg I, Zilberg D. Translating the diatom-grazer defense mechanism to antiparasitic treatment for monogenean infection in guppies. Algal Res. 2021;58:102426.DOI: 10.1016/j.algal.2021.102426.

Wright MH, Paape D, Storck EM, Serwa RA, Smith DF, Tate EW. Global analysis of protein N-myristoylation and exploration of N-myristoyltransferase as a drug target in the neglected human pathogen Leishmania donovani. Chem Biol. 2015;22(3):342-354.DOI: 10.1016/j.chembiol.2015.01.003.

Price HP, Güther MLS, Ferguson MA, Smith DF. Myristoyl-CoA: protein N-myristoyltransferase depletion in trypanosomes causes avirulence and endocytic defects. Mol Biochem Parasitol. 2010;169(1):55-58.DOI: 10.1016/j.molbiopara.2009.09.006.

Price HP, Menon MR, Panethymitaki C, Goulding D, McKean PG, Smith DF. Myristoyl-CoA: protein N-myristoyltransferase, an essential enzyme and potential drug target in kinetoplastid parasites. J Biol Chem. 2003;278(9):7206-7214.DOI: 10.1074/jbc.M211391200.

Grogl M, Thomason TN, Franke ED. Drug resistance in leishmaniasis: its implication in systemic chemotherapy of cutaneous and mucocutaneous disease. Am J Trop Med Hyg. 1992;47(1):117-126.DOI: 10.4269/ajtmh.1992.47.117.

Olías-Molero AI, de la Fuente C, Cuquerella M, Torrado JJ, Alunda JM. Antileishmanial drug discovery and development: time to reset the model? Microorganisms. 2021;9(12):2500,1-18.DOI: 10.3390/microorganisms9122500.

Schlagenhauf E, Etges R, Metcalf P. The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63). Structure. 1998;6(8):1035-1046.DOI: 10.1016/s0969-2126(98)00104-x.

Ferreira GE, dos Santos BN, Dorval ME, Ramos TP, Porrozzi R, Peixoto AA, et al. The genetic structure of Leishmania infantum populations in Brazil and its possible association with the transmission cycle of visceral leishmaniasis. PloS One. 2012;7(5):e36242,1-10.DOI: 10.1371/journal.pone.0036242.

Ferrer-Casal M, Li C, Galizzi M, Stortz CA, Szajnman SH, Docampo R, et al. New insights into molecular recognition of 1,1-bisphosphonic acids by farnesyl diphosphate synthase. Bioorg Med Chem. 2014;22(1):398-405.DOI: 10.1016/j.bmc.2013.11.010.

Källberg M, Wang H, Wang S, Peng J, Wang Z, Lu H, et al. Template-based protein structure modeling using the RaptorX web server. Nat Protoc. 2012;7(8):1511-1522.DOI: 10.1038/nprot.2012.085.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 2019;47(D1):D1102-D1109.DOI: 10.1093/nar/gky1033.

Yildirim A, Mavi A, Oktay M, Kara AA, Algur OF, Bilaloglu V. Comparison of antioxidant and antimicrobial activities of tilia (Tilia argentea Desf ex DC), sage (Salvia triloba L.), and black tea (Camellia sinensis) extracts. J Agric Food Chem. 2000;48(10):5030-5034.DOI: 10.1021/jf000590k.

Mothana RA, Al-Musayeib NM, Al-Ajmi MF, Cos P, Maes L. Evaluation of the in vitro antiplasmodial, antileishmanial, and antitrypanosomal activity of medicinal plants used in Saudi and Yemeni traditional medicine. Evid Based Complement Alternat Med. 2014;2014:905639,1-8.DOI: 10.1155/2014/905639.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res. 2000;28(1):235-242.DOI: 10.1093/nar/28.1.235.

Shaukat A, Mirza H, Ansari A, Yasinzai M, Zaidi S, Dilshad S, et al. Benzimidazole derivatives: synthesis, leishmanicidal effectiveness, and molecular docking studies. Med Chem Res. 2012;22:3606-3620.DOI: 10.1007/s00044-012-0375-5.

Mercado-Camargo J, Cervantes-Ceballos L, Vivas-Reyes R, Pedretti A, Serrano-García ML, Gómez-Estrada H. Homology modeling of leishmanolysin (gp63) from Leishmania panamensis and molecular docking of flavonoids. ACS Omega. 2020;5(24):14741-14749.DOI: 10.1021/acsomega.0c01584.

Aripirala S, Gonzalez-Pacanowska D, Oldfield E, Kaiser M, Amzel LM, Gabelli SB. Structural and thermodynamic basis of the inhibition of Leishmania major farnesyl diphosphate synthase by nitrogen-containing bisphosphonates. Acta Crystallogr D Biol Crystallogr. 2014;70(Pt 3):802-810.DOI: 10.1107/s1399004713033221.

de Mattos Oliveira L, Araújo JSC, Bacelar Costa Junior D, Santana IB, Duarte AA, Leite FHA, et al. Pharmacophore modeling, docking and molecular dynamics to identify Leishmania major farnesyl pyrophosphate synthase inhibitors. J Mol Model. 2018;24(11):314,1-12.DOI: 10.1007/s00894-018-3838-x.

Gadelha APR, Brigagao CM, da Silva MB, Rodrigues ABM, Guimarães ACR, Paiva F, et al. Insights about the structure of farnesyl diphosphate synthase (FPPS) and the activity of bisphosphonates on the proliferation and ultrastructure of Leishmania and Giardia. Parasit Vectors. 2020;13(1):168,1-18.DOI: 10.1186/s13071-020-04019-z.

Brannigan JA, Smith BA, Yu Z, Brzozowski AM, Hodgkinson MR, Maroof A, et al. N-myristoyltransferase from Leishmania donovani: structural and functional characterisation of a potential drug target for visceral leishmaniasis. J Mol Biol. 2010;396(4):985-999.DOI: 10.1016/j.jmb.2009.12.032.

Orabi MAA, Alshahrani MM, Sayed AM, Abouelela ME, Shaaban KA, Abdel-Sattar ES. Identification of potential leishmania N-myristoyltransferase inhibitors from Withania somnifera (L.) Dunal: a molecular docking and molecular dynamics investigation. Metabolites. 2023;13(1):93,1-25.DOI: 10.3390/metabo13010093.

Hussein NN, Al-Azawi K, Sulaiman GM, Albukhaty S, Al-Majeed RM, Jabir M, et al. Silver-cored Ziziphus spina-christi extract-loaded antimicrobial nanosuspension: overcoming multidrug resistance. Nanomedicine (Lond). 2023;18(25):1839-1854.DOI: 10.2217/nnm-2023-0185.

Anyanwu MU, Okoye RC. Antimicrobial activity of Nigerian medicinal plants. J Intercult Ethnopharmacol. 2017;6(2):240-259.DOI: 10.5455/jice.20170106073231.

Duraipandiyan V, Ayyanar M, Ignacimuthu S. Antimicrobial activity of some ethnomedicinal plants used by Paliyar tribe from Tamil Nadu, India. BMC Complement Altern Med. 2006;6:35,1-7.DOI: 10.1186/1472-6882-6-35

Ertürk Ö. Antibacterial and antifungal effects of alcoholic extracts of 41 medicinal plants growing in Turkey. Czech J. Food Sci. 2010;28(1):53-60.DOI: 10.17221/144/2008-CJFS.

Tabefam M, Farimani MM, Danton O, Ramseyer J, Kaiser M, Ebrahimi SN, et al. Antiprotozoal diterpenes from Perovskia abrotanoides. Planta Med. 2018;84(12-13):913-919.DOI: 10.1055/a-0608-4946.

Iqbal K, Iqbal J, Staerk D, Kongstad KT. Characterization of antileishmanial compounds from Lawsonia inermis L. leaves using semi-high resolution antileishmanial profiling combined with HPLC-HRMS-SPE-NMR. Front Pharmacol. 2017;8:337,1-7.DOI: 10.3389/fphar.2017.00337.

Zhan J, He F, Cai H, Wu M, Xiao Y, Xiang F, et al. Composition and antifungal mechanism of essential oil from Chrysanthemum morifolium cv. Fubaiju. J Funct Foods. 2021;87:104746,1-8.DOI: 10.1016/j.jff.2021.104746.

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem substance and compound databases. Nucleic Acids Res. 2016;44(D1):D1202-D1213.DOI: 10.1093/nar/gkv951.

Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF chimera-a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605-1612.DOI: 10.1002/jcc.20084.

Shravani S. Pawar SHR. Review on discovery studio: an important tool for molecular docking. Asian J Research Chem. 2021;14(1):86-88.DOI: 10.5958/0974-4150.2021.00014.6.

Poroikov VV, Filimonov DA, Gloriozova TA, Lagunin AA, Druzhilovskiy DS, Rudik AV, et al. Computer-aided prediction of biological activity spectra for organic compounds: the possibilities and limitations. Russ Chem Bull. 2019;68(12):2143-2154.DOI: 10.1007/s11172-019-2683-0.

Maunz A, Gütlein M, Rautenberg M, Vorgrimmler D, Gebele D, Helma C. lazar: a modular predictive toxicology framework. Front Pharmacol. 2013;4:38,1-10.DOI: 10.3389/fphar.2013.00038.

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7(1):42717,1-13.DOI: 10.1038/srep42717.

Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, et al. GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1-2:19-25.DOI: 10.1016/j.softx.2015.06.001

Alimardan Z, Abbasi M, Khodarahmi G, Kashfi K, Hasanzadeh F, Mahmud A. Identification of new small molecules as dual FoxM1 and Hsp70 inhibitors using computational methods. Res Pharm Sci. 2022;17(6):635-656.DOI: 10.4103/1735-5362.359431.

Valdés-Tresanco MS, Valdés-Tresanco ME, Valiente PA, Moreno E. gmx_MMPBSA: a new tool to perform end-state free energy calculations with GROMACS. J Chem Theory Comput. 2021;17(10):6281-6291.DOI: 10.1021/acs.jctc.1c00645.

Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13(4):581-589.DOI: 10.1359/jbmr.1998.13.4.581.

Torres-Santos E, Lopes D, Oliveira R, Carauta JPP, Falcao C, Kaplan MAC, et al. Antileishmanial activity of isolated triterpenoids from Pourouma guianensis. Phytomedicine. 2004;11(2-3):114-120.DOI: 10.1078/0944-7113-00381.

Mesa C, Blandón G, Muñoz D, Muskus C, Florez A, Ochoa R, et al. In silico screening of potential drug with antileishmanial activity and validation of their activity by in vitro and in vivo studies. J Chem Chem Eng. 2015;9:375-402.DOI: 10.17265/1934-7375/2015.06.002.

Mojallal-Tabatabaei Z, Foroumadi P, Toolabi M, Goli F, Moghimi S, Kaboudanian-Ardestani S, et al. 2-(Bipiperidin-1-yl)-5-(nitroaryl)-1,3,4-thiadiazoles: synthesis, evaluation of in vitro leishmanicidal activity, and mechanism of action. Bioorg Med Chem. 2019;27(16):3682-3691.DOI: 10.1016/j.bmc.2019.07.009.

Qureshi KA, Al Nasr I, Koko WS, Khan TA, Fatmi MQ, Imtiaz M, et al. In vitro and in silico approaches for the antileishmanial activity evaluations of actinomycins isolated from novel Streptomyces smyrnaeus strain UKAQ_23. Antibiotics (Basel). 2021;10(8),887,1-17.DOI: 10.3390/antibiotics10080887.

Badirzadeh A, Taheri T, Taslimi Y, Abdossamadi Z, Heidari-Kharaji M, Gholami E, et al. Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites. PLoS Negl Trop Dis. 2017;11(7):e0005774,1-22.DOI: 10.1371/journal.pntd.0005774.

Heidari-Kharaji M, Badirzadeh A, Khadir F, Soori M. Herbal drugs with promising anti-leishmanial activity: new hope for leishmaniasis treatment. J Skin Stem Cell. 2016;3(2):e66527.DOI: 10.5812/jssc.66527.

Miguel DC, Yokoyama-Yasunaka JK, Uliana SR. Tamoxifen is effective in the treatment of Leishmania amazonensis infections in mice. PLoS Negl Trop Dis. 2008;2(6):e249,1-5. DOI: 10.1371/journal.pntd.0000249.

Montoya A, Daza A, Muñoz D, Ríos K, Taylor V, Cedeño D, et al. Development of a novel formulation with hypericin to treat cutaneous leishmaniasis based on photodynamic therapy in in vitro and in vivo studies. Antimicrob Agents Chemother. 2015;59(9):5804-5813.DOI: 10.1128/aac.00545-15.

Singh S, Sarma S, Katiyar SP, Das M, Bhardwaj R, Sundar D, et al. Probing the molecular mechanism of hypericin-induced parasite death provides insight into the role of spermidine beyond redox metabolism in Leishmania donovani. Antimicrob Agents Chemother. 2015;59(1):15-24.DOI: 10.1128/aac.04169-14.

Sepúlveda AAL, Arenas Velásquez AM, Patiño Linares IA, de Almeida L, Fontana CR, Garcia C, et al. Efficacy of photodynamic therapy using TiO2 nanoparticles doped with Zn and hypericin in the treatment of cutaneous Leishmaniasis caused by Leishmania amazonensis. Photodiagnosis Photodyn Ther. 2020;30:101676.DOI: 10.1016/j.pdpdt.2020.101676.

Rizk YS, Santos-Pereira S, Gervazoni L, Hardoim DJ, Cardoso FO, de Souza C, et al. Amentoflavone as an ally in the treatment of cutaneous Leishmaniasis: analysis of its antioxidant/prooxidant mechanisms. Front Cell Infect Microbiol. 2021;11:615814,1-13.DOI: 10.3389/fcimb.2021.615814.

Rizk YS, Hardoim DdJ, Santos KBA, Zaverucha-do-Valle T, Taniwaki NN, Almeida-Souza F, et al. Amentoflavone isolated from Selaginella sellowii Hieron induces mitochondrial dysfunction in Leishmania amazonensis promastigotes. Parasitol Int. 2022;86:102458. DOI: 10.1016/j.parint.2021.102458.

Chen L, Fang B, Qiao L, Zheng Y. Discovery of anticancer activity of amentoflavone on esophageal squamous cell carcinoma: bioinformatics, structure-based virtual screening, and biological evaluation. J Microbiol Biotechnol. 2022;32(6):718-729. DOI: 10.4014/jmb.2203.03050.

Hossain R, Mahmud S, Khalipha ABR, Saikat ASM, Dey D, Khan RA, et al. Amentoflavone derivatives against SARS-CoV-2 main protease (M PRO): an in silico study. Main Group Chem. 2023;22:313-327. DOI: 10.3233/MGC-220077.

Garcia AR, Amaral ACF, Azevedo MMB, Corte-Real S, Lopes RC, Alviano CS, et al. Cytotoxicity and anti-Leishmania amazonensis activity of Citrus sinensis leaf extracts. Pharm Biol. 2017;55(1):1780-1486.DOI: 10.1080/13880209.2017.1325380.

Macedo SRA, Ferreira AS, de Barros NB, de Oliveira Meneguetti DU, Facundo VA, Shibayama TY, et al. Evaluation of the antileishmanial activity of biodegradable microparticles containing a hexanic eluate subfraction of Maytenus guianensis bark. Exp Parasitol. 2019;205:107738.DOI: 10.1016/j.exppara.2019.107738.

Shi B, Liu S, Huang A, Zhou M, Sun B, Cao H, et al. Revealing the mechanism of Friedelin in the treatment of ulcerative colitis based on network pharmacology and experimental verification. Evid Based Complement Alternat Med. 2021;2021:4451779,1-14. DOI: 10.1155/2021/4451779.

Tu E-C, Hsu W-L, Tzen JTC. Strictinin, a major ingredient in Yunnan Kucha tea possessing inhibitory activity on the infection of mouse hepatitis virus to mouse L cells. Molecules. 2023;28(3):1080,1-15.DOI: 10.3390/molecules28031080.

Mahmoudvand H, Sharififar F, Sharifi I, Ezatpour B, Fasihi Harandi M, Makki MS, et al. In vitro inhibitory effect of Berberis vulgaris (Berberidaceae) and its main component, berberine against different Leishmania species. Iran J Parasitol. 2014;9(1):28-36.PMID: 25642257.

Martín-Quintal Z, Moo-Puc R, González-Salazar F, Chan-Bacab MJ, Torres-Tapia LW, Peraza-Sánchez SR. In vitro activity of Tridax procumbens against promastigotes of Leishmania mexicana. J Ethnopharmacol. 2009;122(3):463-467.DOI: 10.1016/j.jep.2009.01.037.

Et-Touys A, Fellah H, Sebti F, Mniouil M, Aneb Mh, Elboury H, et al. In vitro antileishmanial activity of extracts from endemic Moroccan medicinal plant Salvia verbenaca (L.) Briq. ssp verbenaca Maire (S. clandestina Batt. non L). Eur J Med Plant. 2016;16(1):1-8.DOI: 10.9734/EJMP/2016/27891.

Ezatpour B, Saedi Dezaki E, Mahmoudvand H, Azadpour M, Ezzatkhah F. In vitro and in vivo antileishmanial effects of Pistacia khinjuk against Leishmania tropica and Leishmania major. Evid Based Complement Alternat Med. 2015;2015:149707,1-6.DOI: 10.1155/2015/149707.

Al Nasr IS. Evaluation of the in vitro antileishmanial activities of bioactive guided fractionations of two medicinal plants. Trop Biomed. 2020;37(1):15-23.PMID: 33612714.

Andrade MA, Azevedo CD, Motta FN, Santos ML, Silva CL, Santana JM, et al. Essential oils: in vitro activity against Leishmania amazonensis, cytotoxicity and chemical composition. BMC Complement Altern Med. 2016;16(1):444,1-8.DOI: 10.1186/s12906-016-1401-9

Tabari MA, Youssefi MR, Moghaddas E, Ebrahimi MA, Mousavi NN, Naseri A. Antileishmanial activity of Artemisia sieberi essential oil against Leishmania infantum in vitro. Adv Herb Med. 2017;3(2):40-46.

Moshfe A, Karami K, Bahmani M, Naghmachi M, Askarian S, Rezaei A, et al. Anti leishmanial effect of Plantago psyllium (Ovate) and white vinegar on Leishmania major lesion in BALB/c mice. Iran J Arthropod Borne Dis. 2022;16(1):45-50.DOI: 10.18502/jad.v16i1.11191.

Mardani H, Khalili B, Saberi S, Lorogooini Z, Ghaderi M, Abdizadeh R. Effect of hydroalcoholic extracts of flower and fruit peel of Punica granatum on Leishmania major promastigotes in vitro. Adv Herb Med. 2020;6:32-48

Li Y, Hao Y, Gao B, Geng P, Huang H, Yu L, et al. Chemical profile and in vitro gut microbiota modulatory, anti-inflammatory and free radical scavenging properties of Chrysanthemum morifolium cv. Fubaiju. J Funct Foods. 2019;58:114-122.DOI: 10.1016/j.jff.2019.04.053.

Ellafi A, Farhat R, Snoussi M, Noumi E, Anouar EH, Ben Ali R, et al. Phytochemical profiling, antimicrobial, antibiofilm, insecticidal, and anti-leishmanial properties of aqueous extract from Juglans regia L. root bark: in vitro and in silico approaches. Int J Food Prop. 2023;26(1):1079-1097.DOI: 10.1080/10942912.2023.2200561.

Ashoori F, Fakhar M, Goli HR, Mirzaee F, Faridnia R, Kalani H, et al. Antileishmanial and antibacterial activities of the hydroalcoholic extract of Rhus coriaria L. Ann Parasitol. 2020;62(2): 157-163.DOI: 10.17420/ap6602.250.

ÜLger ST, DelİAlİOĞLu N, GÜLtekİN EO, Aslan G, Yabalak E, ÜLger M, et al. In vitro antileishmanial effect of the plant extracts from Aloe vera (L.) Burm.f. and hypericum perforatum l. leaves. Kafkas Univ Vet Fak Derg. 2021;27(3):363-370.DOI: 10.9775/kvfd.2021.25633.

Tasdemir D, Kaiser M, Brun R, Yardley V, Schmidt TJ, Tosun F, et al. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies. Antimicrob Agents Chemother. 2006;50(4):1352-1364.DOI: 10.1128/aac.50.4.1352-1364.2006.


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