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Scientific Electronic Archives
Health Science
DOI: 10.36560/17420241946
Submitted: 2024-04-13
Published: 2024-06-28

In silico studies (ADME) and in vitro evaluation of the cytotoxic and antimicrobial properties of thiosemicarbazones and thiazole compounds

Federal University of Pernambuco
Federal University of Pernambuco
Federal University of Pernambuco
Federal University of Pernambuco
Federal University of Pernambuco
Federal University of Pernambuco
Federal University of Pernambuco
Federal University of Pernambuco
thiosemicarbazone; thiazole, antimicrobial

Abstract

The thiosemicarbazones and thiazoles are known for their versatility of biological activities, among which we can mention: antioxidant, antimicrobial, anticancer activity and the ability to interact with biological macromolecules, HSA and DNA. This study presented two series of molecules 4-(3-(4-nitrophenyl)-4-phenylthiazol-2(3H)-ylidene)-hydrazine)-methyl)-phenol and 4-(3-(4-chlorophenyl)-4 -phenylthiazol-2(3H)-ylidene)-hydrazine)-methyl)-phenol with biological potential against different microorganisms. The in silico ADME profile showed that thiosemicarbazones and thiazoles have good oral bioavailability. The cytotoxicity results in J774 macrophages cells showed that the compounds showed toxicity ranging from 49.15 to 61.28 µM for thiosemicarbazones and from 10.75 to 39.76 µM for thiazoles. Finally, all thiosemicarbazones and thiazoles synthesized were also able to inhibit microbial growth. In yeasts of the genus Candidas sp. we obtained close results ranging from 12.5 to 50 µg/mL. This study demonstrates that the compounds assessed have the potential to be antimicrobial agents in vitro

References

  1. Ahmed AEM ET AL. 2021. Synthesis, spectral characterization, antimicrobial evaluation and molecular docking studies of new Cu (II), Zn (II) thiosemicarbazone based on sulfonyl isatin. J. Mol. Struct. 1251 132004–4. https://doi.org/10.1016/j.molstruc.2021.132004.
  2. Aliança ASS ET AL. 2017. In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives. Eur J Pharm Sci Jul;105 1–10. https://doi.org/10.1016/j.ejps.2017.05.005.
  3. Althagafi I, El-Metwaly N, Farghaly TA. 2019. New Series of Thiazole Derivatives: Synthesis, Structural Elucidation, Antimicrobial Activity, Molecular Modeling and MOE Docking. Molecules 24 1741 https://doi.org/10.3390/molecules24091741.
  4. Oliveira AR ET AL. 2021. Synthesis, anticancer activity and mechanism of action of new phthalimido-1,3-thiazole derivatives. Eur J Med Chem 347 109597–7. https://doi.org/10.1016/j.cbi.2021.109597.
  5. Ayati A ET AL 2015. Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. Eur J Med Chem Chemistry 97 699–718. https://doi.org/10.1016/j.ejmech.2015.04.015.
  6. Lambertucci C ET AL. New potent and selective A1 adenosine receptor antagonists as potential tools for the treatment of gastrointestinal diseases. Eur J Med Chem 151 199–213. https://doi.org/10.1016/j.ejmech.2018.03.067.
  7. Sharma CS ET AL. 2010. Rajesh Kumar Nema, Vinod Kumar Sharma. Synthesis, anticonvulsant activity and in silico study of some novel amino acids incorporated bicyclo compounds. S J Pharm Sci. 12 42–7 https://doi.org/10.3329/sjps.v2i2.2607.
  8. CLSI 2018. Performance Standards for Antimicrobial Susceptibility Testing. CLSI supplement M60. Wayne, PA: Clinical and Laboratory Standards Institute.
  9. CLSI 2017. Performance Standards for Antimicrobial Susceptibility Testing. 27th ed. CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute.Coates ARM ET AL. 2020. Antibiotic combination therapy against resistant bacterial infections: synergy, rejuvenation and resistance reduction. Expert Rev Anti Infect Ther 18 5–15 https://doi.org/10.1080/14787210.2020.1705155.
  10. Daina A, Michielin O, Zoete V. 2017. SwissADME: a Free web Tool to Evaluate pharmacokinetics, drug-likeness and Medicinal Chemistry Friendliness of Small Molecules. Sci Rep 7 1-13 https://doi.org/10.1038/srep42717.
  11. Eğlence-Bakır S ET AL. 2021. Dioxomolybdenum(VI) complexes with 4-benzyloxysalicylidene-N/S-alkyl thiosemicarbazones: Synthesis, structural analysis, antioxidant activity and xanthine oxidase inhibition. Polyhedron. 209 115467. https://doi.org/10.1016/j.poly.
  12. El-Achkar GA ET AL. 2015. Thiazole derivatives as inhibitors of cyclooxygenases in vitro and in vivo. J Med Chem 750 66–73 https://doi.org/10.1016/j.ejphar.2015.01.008.
  13. Ertl P, Rohde B, Selzer P. 2000. Fast Calculation of Molecular Polar Surface Area as a Sum of Fragment-Based Contributions and Its Application to the Prediction of Drug Transport Properties. J Med Chem 43 37 14–7 https://doi.org/10.1021/jm000942e.
  14. Ferreira E ET AL. 2021. Novel indole-thiazole and indole-thiazolidinone derivatives as DNA groove binders. Int J Biol Macromol 170 622–35 https://doi.org/10.1016/j.ijbiomac.2020.12.153.
  15. Jacob ÍTT, Gomes FOS, Miranda, de V, da J, Peixoto CA, et al. Anti-inflammatory activity of novel thiosemicarbazone compounds indole-based as COX inhibitors. Pharmacol Rep 2021 Feb 15;73(3):907–25. doi:10.1007/s43440-021-00221-7.
  16. Jones RN. Microbiological Features of Vancomycin in the 21st Century: Minimum Inhibitory Concentration Creep, Bactericidal/Static Activity, and Applied Breakpoints to Predict Clinical Outcomes or Detect Resistant Strains. Clinical Infectious Diseases [Internet]. 2006 Jan 1;42(Supplement_1):S13–24. Available from: https://academic.oup.com/cid/article/42/Supplement_1/S13/275219.
  17. Kar S, Chatterjee S. In Silico Meets In Vitro Techniques in ADMET Profiling of Drug Discovery (Part II). Curr Drug Metab. 2021 Sep 14;22(7):502–2. doi:10.2174/138920022207210812124757.
  18. Kayathi Narendra babu, Ummadi Nagarjuna, Guda Dinneswara Reddy, Adivireddy Padmaja, Venkatapuram Padmavathi. Synthesis and antimicrobial activity of benzazolyl azolyl urea derivatives. J Mol Struct. 2019 Dec 1;1198:126871–1. doi:10.1016/j.molstruc.2019.126871.
  19. Kaur Manjal S, Kaur R, Bhatia R, Kumar K, Singh V, Shankar R, et al. Synthetic and medicinal perspective of thiazolidinones: A review. Bioorg Chem. 2017 Dec;75:406–23. doi: 10.1016/j.bioorg.2017.10.014.
  20. Khan SA, Asiri AM. Multi-step synthesis, spectroscopic studies of biological active steroidal thiosemicarbazones and their palladium (II) complex as macromolecules. Int J Biol Macromol 2018 Feb 1;107:105–11. doi:10.1016/j.ijbiomac.2017.08.141.
  21. Kumar A, Kini SG, Rathi E. A Recent Appraisal of Artificial Intelligence and In Silico ADMET Prediction in the Early Stages of Drug Discovery. Mini Rev Med Chem. 2021 Nov 1;21(18):2788–800. doi:10.2174/1389557521666210401091147.
  22. Leigh M, Raines DJ, Castillo CE, Duhme-Klair AK. Inhibition of Xanthine Oxidase by Thiosemicarbazones, Hydrazones and Dithiocarbazates Derived from Hydroxy-Substituted Benzaldehydes. ChemMedChem. 2011 Apr 8;6(6):1107–18.doi: 10.1002/cmdc.201100054.
  23. Leite ACL, Espíndola JWP, de Oliveira Cardoso MV, de Oliveira Filho GB. Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases. Current Medicinal Chemistry. 2019 Oct 10;26(23):4323–54.
  24. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews [Internet]. 1997 Jan;23(1-3):3–25. Available from: https://www.sciencedirect.com/science/article/pii/S0169409X96004231.
  25. Oliveira, J. F., da Silva, A. L., Vendramini-Costa, D. B., da Cruz Amorim, C. A., Campos, J. F., Ribeiro, A. G., ... & de Lima, M. D. C. A. (2015). Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities. Eur J Med Chem Chemistry 104, 148-156. doi:10.1016/j.ejmech.2015.09.036.
  26. Oliveira Filho GB, Cardoso MV de O, Espíndola JWP, Oliveira e Silva DA, Ferreira RS, Coelho PL, et al. Structural design, synthesis and pharmacological evaluation of thiazoles against Trypanosoma cruzi. Eur J Med Chem Chemistry. 2017 Dec;141:346–61.doi:10.1016/j.ejmech.2017.09.047.
  27. Matsa R, Makam P, Kaushik M, Hoti SL, Kannan T. Thiosemicarbazone derivatives: Design, synthesis and in vitro antimalarial activity studies. Eur J Pharm Sci 2019 Sep;137:104986. doi: 10.1016/j.ejps.2019.104986.
  28. Mishra CB, Kumari S, Tiwari M. Thiazole: A promising heterocycle for the development of potent CNS active agents. Eur J Med Chem Chemistry. 2015 Mar;92:1–34.Eur J Med Chem 92 1-34. doi:10.1016/j.ejmech.2014.12.031.
  29. Murray CJ. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet [Internet]. 2022 Jan 19;399(10325):629–55. Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext.
  30. Nag P, Sadani K, Mukherji S, Mukherji S. Beta-lactam antibiotics induced bacteriolysis on LSPR sensors for assessment of antimicrobial resistance and quantification of antibiotics. Sensors and Actuators B: Chemical. 2020 May;311:127945. doi:10.1016/j.snb.2020.127945.
  31. Nastasă C, Tiperciuc B, Duma M, Benedec D, Oniga O. New Hydrazones Bearing Thiazole Scaffold: Synthesis, Characterization, Antimicrobial, and Antioxidant Investigation. Molecules. 2015 Sep 18;20(9):17325–38. doi:10.3390/molecules200917325.
  32. Pham VH, Phan TPD, Phan DC, Vu BD. Synthesis and Bioactivity of Thiosemicarbazones Containing Adamantane Skeletons. Molecules. 2020 Jan 13;25(2):324. doi:10.3390/molecules25020324.
  33. Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. Journal of Medicinal Chemistry [Internet]. 2015 Apr 22;58(9):4066–72. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434528/#ref1.
  34. Prajapati NP, Patel K, Patel HD, Rajani D. Thiazole fused thiosemicarbazones: Microwave-assisted synthesis, biological evaluation and molecular docking study. J Mol Struct. 2019 Mar 5;1179:401–10. https://doi.org/10.1016/j.molstruc.2018.11.025.
  35. Pund AA, Shaikh MH, Chandak BG, Bhosale VN, Magare BK. Pyridine-1,3,4-Thiadiazole-Schiff Base Derivatives, as Antioxidant and Antimitotic Agent: Synthesis and in Silico ADME Studies. Polycycl Aromat Compd. 2022 Jan 17;1–16. doi:10.1080/10406638.2022.2026988.
  36. Sibuh BZ, Gupta PK, Taneja P, Khanna S, Sarkar P, Pachisia S, et al. Synthesis, In Silico Study, and Anti-Cancer Activity of Thiosemicarbazone Derivatives. Biomedicines. 2021 Oct 1;9(10): 1375.doi: 10.3390/biomedicines9101375.
  37. Silva AA, Maia PI da S, Lopes CD, de Albuquerque S, Valle MS. Synthesis, characterization and antichagasic evaluation of thiosemicarbazones prepared from chalcones and dibenzalacetones. Journal of Molecular Structure [Internet]. 2021 May 15 [cited 2021 Oct 7];1232:130014. Available from: https://www.sciencedirect.com/science/article/pii/S0022286021001459.
  38. Sultan B. S, Nurettin S. Poly((Thiazol-2-yl) acrylamide), p(ATA) microgel: Synthesis, characterization and versatile applications. Colloids and Surfaces A. Physicochem Eng. 2017 Jun 1;522:272–8. doi:10.1016/j.colsurfa.2017.03.005.
  39. Trotsko N, Kosikowska U, Paneth A, Plech T, Malm A, Wujec M. Synthesis and Antibacterial Activity of New Thiazolidine-2,4-dione-Based Chlorophenylthiosemicarbazone Hybrids. Molecules. 2018 Apr 26;23(5):1023. doi:10.3390/molecules23051023.
  40. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates. Journal of Medicinal Chemistry [Internet]. 2002 Jun;45(12):2615–23. Available from: https://pdfs.semanticscholar.org/8493/576a7927322ebb79c353bc1c1100a186eb50.pdf.
  41. Vila-Costa M, Gioia R, Jaume Aceña, Pérez S, Casamayor EO, Dachs J. Degradation of sulfonamides as a microbial resistance mechanism. Water Res 2017 May 15; 115:309–17, doi: 10.1016/j.watres.2017.03.007.
  42. Victorio R, Andricopulo AD. Modelagem Molecular de Fármacos. Rev Proc Qui. 2008 Jul 1;2(4):24–36. doi:10.19142/rpq.v2i4.66.
  43. Wang Q, Hamilton PB, Kang F, Zhu X, Zhang Y, Zhao H. Regional-scale investigation for microbial competition-through-environment interactions modulating antibiotic resistance. Sci Total Environ 2020 Sep;734:139341, doi: 10.1016/j.scitotenv.2020.139341.
  44. WORLD HEALTH ORGANIZATION (WHO). 2017. Global Priority List of Antibiotic-Resistant Bacteria To Guide Research, Discovery, And Developmentof New Antibiotics. Disponível em: https://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-ET_NM_WHO.pdf

How to Cite

Nascimento, P. H. do B., Lemos, A. C. A., Santa Clara Marques, D., Neves, R. P., Paz, M. D. S. B., Cruz Filho, I. J. da, … Lima, M. do C. A. de. (2024). In silico studies (ADME) and in vitro evaluation of the cytotoxic and antimicrobial properties of thiosemicarbazones and thiazole compounds . Scientific Electronic Archives, 17(4). https://doi.org/10.36560/17420241946