Synthesis of Ursolic Acid-based Hybrids: In Vitro Antibacterial, Cytotoxicity Studies, In Silico Physicochemical and Pharmacokinetic Properties


Cite item

Full Text

Abstract

Background:Background

Objectives:Amine-linked ursolic acid-based hybrid compounds were prepared in good yields in the range of 60-68%.

Methods:Their molecular structures were successfully confirmed using different spectroscopic methods including 1H/13C NMR, UHPLC-HRMS and FTIR spectroscopy. The in vitro cytotoxicity of some of these hybrid molecules against three human tumour cells, such as MDA-MB23, MCF7, and HeLa was evaluated using the MTT colorimetric method.

Result:Their antibacterial efficacy was evaluated against eleven bacterial pathogens using a serial dilution assay. Majority of the bacterial strains were inhibited significantly by compounds 17 and 24, with the lowest MIC values in the range of 15.3-31.25 µg/mL. Compound 16 exhibited higher cytotoxicity against HeLa cells than ursolic acid, with an IC50 value of 43.64 g/mL.

Conclusion:The in vitro antibacterial activity and cytotoxicity of these hybrid compounds demonstrated that ursolic acid-based hybrid molecules are promising compounds. Further research into ursolic acid-based hybrid compounds is required.

About the authors

Vuyolwethu Khwaza

Department of Chemistry, University of Fort Hare

Email: info@benthamscience.net

Samson Oselusi

School of Pharmacy, University of the Western Cape

Email: info@benthamscience.net

Eric Morifi

School of Chemistry, Mass Spectrometry Division, University of Witwatersrand

Email: info@benthamscience.net

Mutshinyalo Nwamadi

Department of Chemistry, University of Johannesburg

Email: info@benthamscience.net

Kamogelo Hlope

Department of Biochemistry, Microbiology and Biotechnology, Faculty of Science and Agriculture, University of Limpopo

Email: info@benthamscience.net

Derek Ndinteh

Department of Applied Chemistry, University of Johannesburg

Email: info@benthamscience.net

Thabe Matsebatlela

Department of Biochemistry, Microbiology and Biotechnology, Faculty of Science and Agriculture, University of Limpopo

Email: info@benthamscience.net

Opeoluwa Oyedeji

Department of Chemistry, University of Fort Hare

Email: info@benthamscience.net

Blessing Aderibigbe

Department of Chemistry, University of Fort Hare

Author for correspondence.
Email: info@benthamscience.net

References

  1. Xu B, Chu F, Zhang Y, et al. A series of new ligustrazine-triterpenes derivatives as anti-tumor agents: Design, synthesis, and biological evaluation. Int J Mol Sci 2015; 16(9): 21035-55. doi: 10.3390/ijms160921035 PMID: 26404253
  2. Khwaza V, Oyedeji OO, Aderibigbe BA. Ursolic acid-based derivatives as potential anti-cancer agents: an update. Int J Mol Sci 2020; 21(16): 5920. doi: 10.3390/ijms21165920 PMID: 32824664
  3. Xiao S, Wang Q, Si L, et al. Synthesis and anti-HCV entry activity studies of β-cyclodextrin-pentacyclic triterpene conjugates. ChemMedChem 2014; 9(5): 1060-70. doi: 10.1002/cmdc.201300545 PMID: 24623716
  4. Sathya S, Sudhagar S, Sarathkumar B, Lakshmi BS. EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest in breast cancer cells. Life Sci 2014; 95(1): 53-62. doi: 10.1016/j.lfs.2013.11.019 PMID: 24333132
  5. Shanmugam MK, Dai X, Kumar AP, Tan BKH, Sethi G, Bishayee A. Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol 2013; 85(11): 1579-87. doi: 10.1016/j.bcp.2013.03.006 PMID: 23499879
  6. Wolska KI, Grudniak AM, Fiecek B, Kraczkiewiczdowjat A, Kurek A. Antibacterial activity of oleanolic and ursolic acids and their derivatives. Cent Eur J Biol 2010; 5(5): 543-53.
  7. Kazmi I, Rahman M, Afzal M, et al. Anti-diabetic potential of ursolic acid stearoyl glucoside: A new triterpenic gycosidic ester from Lantana camara. Fitoterapia 2012; 83(1): 142-6. doi: 10.1016/j.fitote.2011.10.004 PMID: 22051701
  8. Zhao J, Zheng H, Sui Z, et al. Ursolic acid exhibits anti-inflammatory effects through blocking TLR4-MyD88 pathway mediated by autophagy. Cytokine 2019; 123: 154726. doi: 10.1016/j.cyto.2019.05.013 PMID: 31302461
  9. Tohmé MJ, Giménez MC, Peralta A, Colombo MI, Delgui LR. Ursolic acid: A novel antiviral compound inhibiting rotavirus infection in vitro. Int J Antimicrob Agents 2019; 54(5): 601-9. doi: 10.1016/j.ijantimicag.2019.07.015 PMID: 31356859
  10. Ramachandran S, Prasad NR. Effect of ursolic acid, a triterpenoid antioxidant, on ultraviolet-B radiation-induced cytotoxicity, lipid peroxidation and DNA damage in human lymphocytes. Chem Biol Interact 2008; 176(2-3): 99-107. doi: 10.1016/j.cbi.2008.08.010 PMID: 18793624
  11. Liu MC, Yang SJ, Jin LH, et al. Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety. Eur J Med Chem 2012; 58: 128-35. doi: 10.1016/j.ejmech.2012.08.048 PMID: 23124210
  12. Rashid S, Dar BA, Majeed R, Hamid A, Bhat BA. Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents. Eur J Med Chem 2013; 66: 238-45. doi: 10.1016/j.ejmech.2013.05.029 PMID: 23811086
  13. Kraljević TG, Harej A, Sedić M, et al. Synthesis, in vitro anticancer and antibacterial activities and in silico studies of new 4-substituted 1,2,3-triazole–coumarin hybrids. Eur J Med Chem 2016; 124: 794-808. doi: 10.1016/j.ejmech.2016.08.062 PMID: 27639370
  14. Yusuf K, Sampath V, Umar S. Bacterial Infections and Cancer: Exploring this association and its implications for cancer Patients. Int J Mol Sci 2023; 24(4): 3110. doi: 10.3390/ijms24043110 PMID: 36834525
  15. Gatadi S, Gour J, Nanduri S. Natural product derived promising anti-MRSA drug leads: A review. Bioorg Med Chem 2019; 27(17): 3760-74. doi: 10.1016/j.bmc.2019.07.023 PMID: 31324564
  16. Khwaza V, Oyedeji OO, Aderibigbe BA, et al. Synthesis, antibacterial, and cytotoxicity evaluation of Oleanolic Acid-4-aminoquinoline based hybrid compounds. Recent Adv anti-infective drug Discov 2021; 16(2): 1-15.
  17. Nguyen HT, Thi TA, Thi P, et al. A new approach for the synthesis of novel naphthoquinone chalcone hybrid compounds. Tetrahedron Lett 2021; 81: 153337. doi: 10.1016/j.tetlet.2021.153337
  18. Rea F, Corrao G, Merlino L, Mancia G. Early cardiovascular protection by initial two-drug fixed-dose combination treatment vs. monotherapy in hypertension. Eur Heart J 2018; 39(40): 3654-61. doi: 10.1093/eurheartj/ehy420 PMID: 30060044
  19. Sadaphal P, Chakraborty K, Jassim-AlMossawi H, et al. Rifampicin bioavailability in fixed-dose combinations for tuberculosis treatment: Evidence and Policy Actions. J Lung Health Dise 2019; 3(3): 9-15. doi: 10.29245/2689-999X/2019/3.1155
  20. Wang P, Wang J, Guo T, Li Y. Synthesis and cytotoxic activity of the N-acetylglucosamine-bearing triterpenoid saponins. Carbohydr Res 2010; 345(5): 607-20. doi: 10.1016/j.carres.2010.01.002 PMID: 20116049
  21. Jin IJ, Ko YI, Kim YM, Han SK. Solubilization of oleanolic acid and ursolic acid by cosolvency. Arch Pharm Res 1997; 20(3): 269-74. doi: 10.1007/BF02976156 PMID: 18975163
  22. Wang Z, Barrows RD, Emge TJ, Knapp S. stereochemical aspects of T3P amidations. Org Process Res Dev 2017; 21(3): 399-407. doi: 10.1021/acs.oprd.7b00046
  23. Montalbetti CAGN, Falque V. Amide bond formation and peptide coupling. Tetrahedron 2005; 61(46): 10827-52. doi: 10.1016/j.tet.2005.08.031
  24. Anusionwu CG, Aderibigbe BA, Adeyemi SA, et al. Novel ferrocenylbisphosphonate hybrid compounds: Synthesis, characterization and potent activity against cancer cell lines. Bioorg Med Chem 2022; 58: 116652. doi: 10.1016/j.bmc.2022.116652 PMID: 35180594
  25. Bai KK, Yu Z, Chen FL, Li F, Li WY, Guo YH. Synthesis and evaluation of ursolic acid derivatives as potent cytotoxic agents. Bioorg Med Chem Lett 2012; 22(7): 2488-93. doi: 10.1016/j.bmcl.2012.02.009 PMID: 22370266
  26. Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: Progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58. doi: 10.1038/nrd.2018.168 PMID: 30310233
  27. Yadav V, Talwar P. Biomedicine & Pharmacotherapy Repositioning of fl uoroquinolones from antibiotic to anti-cancer agents : An underestimated truth. Biomed Pharmacother 2019; 111: 934-46. doi: 10.1016/j.biopha.2018.12.119 PMID: 30841473
  28. Matthews H, Usman-Idris M, Khan F, Read M, Nirmalan N. Drug repositioning as a route to anti-malarial drug discovery: Preliminary investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride hydrate. Malar J 2013; 12(1): 359. doi: 10.1186/1475-2875-12-359 PMID: 24107123
  29. Ashley EA, Recht J, White NJ. Primaquine: The risks and the benefits. Malar J 2014; 13(1): 418. doi: 10.1186/1475-2875-13-418 PMID: 25363455
  30. Fernandes I, Vale N, de Freitas V, Moreira R, Mateus N, Gomes P. Anti-tumoral activity of imidazoquines, a new class of antimalarials derived from primaquine. Bioorg Med Chem Lett 2009; 19(24): 6914-7. doi: 10.1016/j.bmcl.2009.10.081 PMID: 19896373
  31. Perković I, Antunović M, Marijanović I, et al. Novel urea and bis -urea primaquine derivatives with hydroxyphenyl or halogenphenyl substituents: Synthesis and biological evaluation. Eur J Med Chem 2016; 124: 622-36. doi: 10.1016/j.ejmech.2016.08.021 PMID: 27614409
  32. Pavić K, Perković I, Gilja P, et al. Design, synthesis and biological evaluation of novel primaquinecinnamic acid conjugates of the amide and acylsemicarbazide type. Molecules 2016; 21(12): 1629. doi: 10.3390/molecules21121629 PMID: 27916811
  33. Vlainić J, Kosalec I, Pavić K, Hadjipavlou-Litina D, Pontiki E, Zorc B. Insights into biological activity of ureidoamides with primaquine and amino acid moieties. J Enzyme Inhib Med Chem 2018; 33(1): 376-82. doi: 10.1080/14756366.2017.1423067 PMID: 29363364
  34. Lanzafame G, Sarakha M, Fabbri D, Vione D. Degradation of methyl 2-aminobenzoate (methyl anthranilate) by H2O2/UV: Effect of inorganic anions and derived radicals. Molecules 2017; 22(4): 619. doi: 10.3390/molecules22040619 PMID: 28417930
  35. Sławiński J, Żołnowska B, Pirska D, Kędzia A, Kwapisz E. Synthesis and antibacterial activity of novel 4-chloro-2-mercaptobenzenesulfonamide derivatives. J Enzyme Inhib Med Chem 2013; 28(1): 41-51. doi: 10.3109/14756366.2011.625024 PMID: 22145585
  36. Zhang X. Syntheses, crystal structures and antibacterial activities of two antipyrine derivatives. J Chem Crystallogr 2011; 41(7): 1044-8. doi: 10.1007/s10870-011-0042-6
  37. Wei W, Yan H, Zhao J, et al. Multi-omics comparisons of p -aminosalicylic acid (PAS) resistance in folC mutated and un-mutated Mycobacterium tuberculosis strains. Emerg Microbes Infect 2019; 8(1): 248-61. doi: 10.1080/22221751.2019.1568179 PMID: 30866779
  38. Minato Y, Thiede JM, Kordus SL, McKlveen EJ, Turman BJ, Baughn AD. Mycobacterium tuberculosis folate metabolism and the mechanistic basis for para-aminosalicylic acid susceptibility and resistance. Antimicrob Agents Chemother 2015; 59(9): 5097-106. doi: 10.1128/AAC.00647-15 PMID: 26033719
  39. Hatnapure GD, Keche AP, Rodge AH, Birajdar SS, Tale RH, Kamble VM. Synthesis and biological evaluation of novel piperazine derivatives of flavone as potent anti-inflammatory and antimicrobial agent. Bioorg Med Chem Lett 2012; 22(20): 6385-90. doi: 10.1016/j.bmcl.2012.08.071 PMID: 22981334
  40. Kim HS, Choi BS, Kwon KC, Lee SO, Kwak HJ, Lee CH. Synthesis and antimicrobial activity of squalamine analogue. Bioorg Med Chem 2000; 8(8): 2059-65. doi: 10.1016/S0968-0896(00)00128-0 PMID: 11003150
  41. Loncle C, Brunel JM, Vidal N, Dherbomez M, Letourneux Y. Synthesis and antifungal activity of cholesterol-hydrazone derivatives. Eur J Med Chem 2004; 39(12): 1067-71. doi: 10.1016/j.ejmech.2004.07.005 PMID: 15571868
  42. Blagbrough IS, Al-Hadithi D, Geall AJ. Cheno-, ursolic and deoxycholic acid spermine conjugates: Relative binding affinities for calf thymus DNA. Tetrahedron 2000; 56(21): 3439-47. doi: 10.1016/S0040-4020(00)00265-9
  43. Jones SR, Kinney WA, Zhang X, Jones LM, Selinsky BS. The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6β-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid. Steroids 1996; 61(10): 565-71. doi: 10.1016/S0039-128X(96)00114-6 PMID: 8910969
  44. Freitag R. Synthetic Polymers for Biotechnology and Medicine. CRC press 2002.
  45. Mallick S, Thuy LT, Lee S, Park JII, Choi JS. Liposomes containing cholesterol and mitochondria-penetrating peptide (MPP) for targeted delivery of antimycin A to A549 cells. Colloids Surf B Biointerfaces 2018; 161: 356-64. doi: 10.1016/j.colsurfb.2017.10.052 PMID: 29100129
  46. Fonkui TY, Ikhile MI, Ndinteh DT, Njobeh PB. Microbial activity of some heterocyclic Schiff bases and metal complexes: A review. Trop J Pharm Res 2019; 17(12): 2507-18. doi: 10.4314/tjpr.v17i12.29
  47. Oselusi SO, Fadaka AO, Wyckoff GJ, Egieyeh SA. computational target-based screening of anti-mrsa natural products reveals potential multitarget mechanisms of action through peptidoglycan synthesis proteins. ACS Omega 2022; 7(42): 37896-906. doi: 10.1021/acsomega.2c05061 PMID: 36312373
  48. Sastry MG, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 2013; 27(3): 221-34. doi: 10.1007/s10822-013-9644-8 PMID: 23579614
  49. Ibrahim RS, El-Banna AA. Network pharmacology-based analysis for unraveling potential cancer-related molecular targets of Egyptian propolis phytoconstituents accompanied with molecular docking and in vitro studies. RSC Advances 2021; 11(19): 11610-26. doi: 10.1039/D1RA01390D PMID: 35423607
  50. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform 2011; 3(1): 33. doi: 10.1186/1758-2946-3-33 PMID: 21982300
  51. Madrid PB, Sherrill J, Liou AP, Weisman JL, DeRisi JL, Guy RK. Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities. Bioorg Med Chem Lett 2005; 15(4): 1015-8. doi: 10.1016/j.bmcl.2004.12.037 PMID: 15686903
  52. Jama S, Nqoro X, Morifi E. 4-Aminosalicylic Acid-based Hybrid Compounds: Synthesis and in vitro Antiplasmodial Evaluation. Lett Drug Des Discov 2021; 18(3): 284-98.
  53. Kahnt M, Hoenke S, Fischer L, Al-Harrasi A, Csuk R. Synthesis and cytotoxicity evaluation of DOTA-conjugates of ursolic acid. Molecules 2019; 24(12): 2254. doi: 10.3390/molecules24122254 PMID: 31212958
  54. Majidzadeh H, Araj-Khodaei M, Ghaffari M, et al. The combination of berberine and methotrexate enhances anti-cancer effects in HeLa cancer cell line: A morphological study. Ulum-i Daruyi 2021; 27(4): 536-42. doi: 10.34172/PS.2021.12
  55. Bandyopadhyay M, Muthuirulan P. promising targets for prospective antibacterial therapy. EC Microbiol 2018; 14(6): 351-60.
  56. Bachran D, Schneider S, Bachran C, et al. Epidermal growth factor receptor expression affects the efficacy of the combined application of saponin and a targeted toxin on human cervical carcinoma cells. Int J Cancer 2010; 127(6): 1453-61. doi: 10.1002/ijc.25123 PMID: 20020492
  57. Sevelda F, Mayr L, Kubista B, et al. EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance. J Exp Clin Cancer Res 2015; 34(1): 134. doi: 10.1186/s13046-015-0251-5 PMID: 26526352
  58. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol 2018; 12(1): 3-20. doi: 10.1002/1878-0261.12155 PMID: 29124875
  59. Masuda H, Zhang D, Bartholomeusz C, Doihara H, Hortobagyi GN, Ueno NT. Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res Treat 2012; 136(2): 331-45. doi: 10.1007/s10549-012-2289-9 PMID: 23073759
  60. Burness ML, Grushko TA, Olopade OI. Epidermal growth factor receptor in triple-negative and basal-like breast cancer: Promising clinical target or only a marker? Cancer J 2010; 16(1): 23-32. doi: 10.1097/PPO.0b013e3181d24fc1 PMID: 20164687
  61. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: Clinical features and patterns of recurrence. Clin Cancer Res 2007; 13(15): 4429-34. doi: 10.1158/1078-0432.CCR-06-3045 PMID: 17671126
  62. Levantini E, Maroni G, Del Re M, Tenen DG. EGFR signaling pathway as therapeutic target in human cancers. Semin Cancer Biol 2022; 85: 253-75. doi: 10.1016/j.semcancer.2022.04.002 PMID: 35427766
  63. Pei Y, Zhang Y, Zheng K, et al. Ursolic acid suppresses the biological function of osteosarcoma cells. Oncol Lett 2019; 18(3): 2628-38. doi: 10.3892/ol.2019.10561 PMID: 31404298
  64. Jabeen M, Ahmad S, Shahid K, Sadiq A, Rashid U. Ursolic acid hydrazide based organometallic complexes: Synthesis, characterization, antibacterial, antioxidant, and docking studies. Front Chem 2018; 6: 1-14.
  65. Oprean C, Mioc M, Csányi E, et al. Improvement of ursolic and oleanolic acids’ antitumor activity by complexation with hydrophilic cyclodextrins. Biomed Pharmacother 2016; 83: 1095-104. doi: 10.1016/j.biopha.2016.08.030 PMID: 27551755
  66. Luan T, Jin C, Jin CM, Gong GH, Quan ZS. Synthesis and biological evaluation of ursolic acid derivatives bearing triazole moieties as potential anti- Toxoplasma gondii agents. J Enzyme Inhib Med Chem 2019; 34(1): 761-72. doi: 10.1080/14756366.2019.1584622 PMID: 30836795
  67. da Silva M, Comin M, Duarte T, et al. Synthesis, antiproliferative activity and molecular properties predictions of galloyl derivatives. Molecules 2015; 20(4): 5360-73. doi: 10.3390/molecules20045360 PMID: 25816079
  68. He Q, Xiao F, Yuan Q, Zhang J, Zhan J, Zhang Z. Cannabinoid receptor 2: A potential novel therapeutic target for sepsis? Acta Clin Belg 2019; 74(2): 70-4. doi: 10.1080/17843286.2018.1461754 PMID: 29694303
  69. Althobiti HA, Zabin SA. New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: Their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties. Open Chem 2020; 18(1): 591-607. doi: 10.1515/chem-2020-0085
  70. Neervannan S. Preclinical formulations for discovery and toxicology: Physicochemical challenges. Expert Opin Drug Metab Toxicol 2006; 2(5): 715-31. doi: 10.1517/17425255.2.5.715 PMID: 17014391
  71. Raj S, Sasidharan S, Dubey VK, Saudagar P. Identification of lead molecules against potential drug target protein MAPK4 from L. donovani: An in-silico approach using docking, molecular dynamics and binding free energy calculation. PLoS One 2019; 14(8): e0221331. doi: 10.1371/journal.pone.0221331 PMID: 31425543
  72. Souza HDS, de Sousa RPF, Lira BF, et al. Synthesis, in silico study and antimicrobial evaluation of new selenoglycolicamides. J Braz Chem Soc 2019; 30(1): 188-97.
  73. Mehboob R. Neurokinin-1 Receptor as a potential drug target for COVID-19 treatment. Biomed Pharmacother 2021; 143: 112159. doi: 10.1016/j.biopha.2021.112159 PMID: 34536760
  74. Rhoades JA, Peterson YK, Zhu HJ, Appel DI, Peloquin CA, Markowitz JS. Prediction and in vitro evaluation of selected protease inhibitor antiviral drugs as inhibitors of carboxylesterase 1: A potential source of drug-drug interactions. Pharm Res 2012; 29(4): 972-82. doi: 10.1007/s11095-011-0637-9 PMID: 22161308
  75. Garnier A, Vykoukal J, Hubertus J, et al. Targeting the neurokinin-1 receptor inhibits growth of human colon cancer cells. Int J Oncol 2015; 47(1): 151-60. doi: 10.3892/ijo.2015.3016 PMID: 25998227
  76. Markowska A, Antoszczak M, Markowska J, Huczyński A. Statins: Hmg-coa reductase inhibitors as potential anticancer agents against malignant neoplasms in women. Pharmaceuticals (Basel) 2020; 13(12): 422. doi: 10.3390/ph13120422 PMID: 33255609
  77. Kostrzewa T, Styszko J, Gorska-Ponikowska M, Sledzinski T, Kuban-Jankowska A. Inhibitors of protein tyrosine phosphatase PTP1B with anticancer potential. Anticancer Res 2019; 39(7): 3379-84. doi: 10.21873/anticanres.13481 PMID: 31262859
  78. Forooshani MK, Scarpitta R, Fanelli GN, Miccoli M, Naccarato AG, Scatena C. Is It time to consider the androgen receptor as a therapeutic target in breast cancer? Anticancer Agents Med Chem 2022; 22(4): 775-86.
  79. Bagchi S, Rathee P, Jayaprakash V, Banerjee S. Farnesyl transferase inhibitors as potential anticancer agents. Mini Rev Med Chem 2018; 18(19): 1611-23. doi: 10.2174/1389557518666180801110342 PMID: 30068272
  80. Ranjbarnejad T, Saidijam M, tafakh M, Pourjafar M, Talebzadeh F, Najafi R. Garcinol exhibits antiproliferative activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells. Hum Exp Toxicol 2017; 36(7): 692-700. doi: 10.1177/0960327116660865 PMID: 27481098

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers