New Thiosemicarbazide Derivatives with Multidirectional Biological Action
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
Compound Number | R | Compound Number | R |
3a | 3d | ||
3b | 3e | ||
3c | 3f |
2.2. Predictions of the Biological Activity
2.3. Anthelmintic Activity
2.4. Antimicrobial Activity
2.5. Anticancer Activity
2.6. Antioxidant Activity
2.7. Lipinski’s Rule of Drug-Likeness
3. Materials and Methods
3.1. Chemistry
3.1.1. The Procedure for the Synthesis of Hydrazide of 3-Trifluoromethylbenzoic Acid (2)
3.1.2. The Procedure for the Synthesis of 1-(3-Trifluoromethylbenzoyl)-4-substituted Thiosemicarbazide (3a–3f)
3.1.3. The Procedure for the Synthesis of 4-(3-Chlorophenyl)-5-(3-trifluoromethylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4)
4-(3-Chlorophenyl)-1-(3-trifluoromethylbenzoyl)thiosemicarbazide (3a)
1-(3-Trifluoromethylbenzoyl)-4-(3-methoxyphenyl)thiosemicarbazide (3b)
4-Butyl-1-(3-trifluoromethylbenzoyl)thiosemicarbazide (3c)
1-(3-Trifluoromethylbenzoyl)-4-(3-methylphenyl)thiosemicarbazide (3d)
1-(3-Trifluoromethylbenzoyl)-4-(3-fluorophenyl)thiosemicarbazide (3e)
1-(3-Trifluoromethylbenzoyl)-4-(phenyl)thiosemicarbazide (3f)
4-(3-Chlorophenyl)-5-(3-trifluoromethylphenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (4)
3.2. Predictions of the Biological Activity
3.3. Anthelmintic Activity Assay
3.4. Antimicrobial Activity Assay
3.5. Anticancer Activity
3.6. Antioxidant Activity
3.6.1. Estimation of Lipid Peroxidation
3.6.2. Statistical Analyses
3.7. The Lipinski Rules
- No more than five hydrogen bond donors (i.e., NH or OH groups);
- No more than ten hydrogen bond acceptors (i.e., N or O atoms);
- A molecular weight of less than 500 Daltons;
- A partition coefficient (log P) of less than 5;
- Molar refractivity ranging from 40 to 130.
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Neglected Tropical Diseases. Available online: https://www.who.int/health-topics/neglected-tropical-diseases#tab=tab_1 (accessed on 4 July 2022).
- CDC. Soil-Transmitted Helminths. Available online: https://www.cdc.gov/parasites/sth/index.html (accessed on 13 July 2022).
- Charlier, J.; Höglund, J.; von Samson-Himmelstjerna, G.; Dorny, P.; Vercruysse, J. Gastrointestinal Nematode Infections in Adult Dairy Cattle: Impact on Production, Diagnosis and Control. Vet. Parasitol. 2009, 164, 70–79. [Google Scholar] [CrossRef] [PubMed]
- Kaplan, R.M. Drug Resistance in Nematodes of Veterinary Importance: A Status Report. Trends Parasitol. 2004, 20, 477–481. [Google Scholar] [CrossRef] [PubMed]
- Baiak, B.H.B.; Lehnen, C.R.; da Rocha, R.A. Anthelmintic Resistance in Cattle: A Systematic Review and Meta-Analysis. Livestock Sci. 2018, 217, 127–135. [Google Scholar] [CrossRef]
- Redman, E.; Whitelaw, F.; Tait, A.; Burgess, C.; Bartley, Y.; Skuce, P.J.; Jackson, F.; Gilleard, J.S. The Emergence of Resistance to the Benzimidazole Anthelmintics in Parasitic Nematodes of Livestock Is Characterised by Multiple Independent Hard and Soft Selective Sweeps. PLoS Neglect. Trop. Dis. 2015, 9, e0003494. [Google Scholar] [CrossRef] [PubMed]
- Fissiha, W.; Kinde, M.Z. Anthelmintic Resistance and Its Mechanism: A Review. Infect. Drug Resist. 2021, 14, 5403. [Google Scholar] [CrossRef] [PubMed]
- Ghassemi, A.; Farhangi, H.; Badiee, Z.; Banihashem, A.; Mosaddegh, M.R. Evaluation of Nosocomial Infection in Patients at Hematology-Oncology Ward of Dr. Sheikh Children’s Hospital. Iran. J. Pediatr. Hematol. Oncol. 2015, 5, 179–185. [Google Scholar]
- Vuong, C.; Otto, M. Staphylococcus epidermidis infections. Microbes Infect. 2002, 4, 481–489. [Google Scholar] [CrossRef] [PubMed]
- Waddington, R.J.; Moseley, R.; Embery, G. Review: Periodontal disease mechanisms. Reactive oxygenspecies: A potential role in the pathogenesis of periodontal diseases. J. Oral Dis. 2000, 6, 138–151. [Google Scholar]
- Ameryckx, A.; Thabault, L.; Pochet, L.; Leimanis, S.; Poupaert, J.H.; Wouters, J.; Joris, B.; Van Bambeke, F.; Frédérick, R. 1-(2-Hydroxybenzoyl)-thiosemicarbazides are promising antimicrobial agents targeting D-alanine-D-alanine ligase in bacterio. Eur. J. Med. Chem. 2018, 159, 324–338. [Google Scholar] [CrossRef]
- Ameryckx, A.; Pochet, L.; Wang, G.; Yildiz, E.; Saadi, B.E.; Wouters, J.; Van Bambeke, F.; Frédérick, R. Pharmacomodulations of the benzoyl-thiosemicarbazide scaffold reveal antimicrobial agents targeting D-alanyl-D-alanine ligase in bacterio. Eur. J. Med. Chem. 2020, 200, 112444. [Google Scholar] [CrossRef]
- Al-Mutairi, A.A.; Al-Alshaikh, M.A.; Al-Omary, F.A.M.; Hassan, H.M.; El-Mahdy, A.M.; El-Emam, A.A. Synthesis, antimicrobial, and anti-proliferative activities of novel 4-(adamantan-1-yl)-1-arylidene-3-thiosemicarbazides, 4-arylmethyl N′-(Adamantan-1-yl)piperidine-1-carbothioimidates, and related derivatives. Molecules 2019, 24, 4308. [Google Scholar] [CrossRef]
- Chen, R.; Huo, L.; Jaiswal, Y.; Huang, J.; Zhong, Z.; Zhong, J.; Williams, L.; Xia, X.; Liang, Y.; Yan, Z. Design, synthesis, antimicrobial, and anticancer activities of acridine thiosemicarbazides derivatives. Molecules 2019, 24, 2065. [Google Scholar] [CrossRef]
- El-Sharief, M.A.M.S.; Abbas, S.Y.; El-Bayouki, K.A.M.; El-Gammal, E.W. Synthesis of thiosemicarbazones derived from N-(4-hippuric acid)thiosemicarbazide and different carbonyl compounds as antimicrobial agents. Eur. J. Med. Chem. 2013, 67, 263–268. [Google Scholar] [CrossRef]
- Wang, Y.; Dang, Q.; Liu, C.; Yu, D.; Pu, X.; Wang, Q.; Gao, H.; Zhang, B.; Cha, D. Selective adsorption toward Hg(II) and inhibitory effect on bacterial growth occurring on thiosemicarbazide-functionalized chitosan microsphere surface. ACS Appl. Mater. Interfaces 2018, 10, 40302–40316. [Google Scholar] [CrossRef]
- Chen, Y.-L.; Fang, K.-C.; Sheu, J.-Y.; Hsu, S.-L.; Tzeng, C.-C. Synthesis and antibacterial evaluation of certain quinolone derivatives. J. Med. Chem. 2001, 44, 2374–2377. [Google Scholar] [CrossRef]
- Devar, S.B.; Swamy, B.H.M.; Rao, B.N.; Shivkumar, H.; Shivkumar, B. Synthesis of new tetrazoloquinoline thiocarbohydrazides as potential antimicrobial agents. Indian J. Heterocycl. Chem. 2011, 21, 37–40. [Google Scholar]
- Umadevi, P.; Deepti, K.; Srinath, I.; Vijayalakshmi, G.; Tarakaramji, M. Synthesis and in-vitro antibacterial activity of some new urea, thiourea and thiosemicarbazide derivatives. Int. J. Pharm. Pharm. Sci. 2012, 4, 379–383. [Google Scholar]
- Pitucha, M.; Karczmarzyk, Z.; Swatko-Ossor, M.; Wysocki, W.; Woś, M.; Chudzik, K.; Ginalska, G.; Fruziński, A. Synthesis, in vitro screening and docking studies of new thiosemicarbazide derivatives as antitubercular agent. Molecules 2019, 24, 251. [Google Scholar] [CrossRef]
- Paneth, A.; Stączek, P.; Plech, T.; Strzelczyk, A.; Dzitko, K.; Wujec, M.; Kuśmierz, E.; Kosikowska, U.; Grzegorczyk, A.; Paneth, P. Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors. J. Enzym. Inhib. Med. Chem. 2016, 31, 14–22. [Google Scholar] [CrossRef]
- Gopalakrishnan, M.; Sureshkumar, P.; Thanusu, J.; Kanagarajan, V. Unusual formation of N-hydroxy-3,3-dimethyl-2,6-diarylpiperidin-4-one and its thiosemicarbazide derivative–synthesis and antimicrobial activity. Pharm. Chem. J. 2008, 42, 271–276. [Google Scholar] [CrossRef]
- Siddiqui, N.; Singh, O. Antibacterial activity of some 4-N-substituted thiosemicarbazides and thiosemicarbazones. Indian J. Pharm. Sci. 2003, 65, 423–425. [Google Scholar]
- Toan, V.N.; Tri, N.M.; Thanh, N.D. Substituted 4-formyl-2H-chromen-2-ones: Their reaction with N-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)thiosemicarbazide, antibacterial and antifungal activity of their thiosemicarbazone products. Curr. Org. Chem. 2020, 24, 2272–2282. [Google Scholar] [CrossRef]
- Molnar, M.; Tomić, M.; Pavić, V. Coumarinyl thiosemicarbazides as antimicrobial agents. Pharm. Chem. J. 2018, 51, 1078–1081. [Google Scholar] [CrossRef]
- Han, M.İ.; İnce, U.; Gündüz, M.G.; Küçükgüzel, Ş.G. Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of New Thiosemicarbazide-Triazole Hybrid Derivatives of (S)-Naproxen. Chem. Biodivers. 2022, 19, e202100900. [Google Scholar] [CrossRef]
- Sriram, D.; Yogeeswari, P.; Thirumurugan, R.; Pavana, R.K. Discovery of new antitubercular oxazolyl thiosemicarbazones. J. Med. Chem. 2006, 49, 3448–3450. [Google Scholar] [CrossRef]
- García, C.C.; Brousse, B.N.; Carlucci, M.J.; Moglioni, A.G.; Alho, M.M.; Moltrasio, G.Y.; Damonte, E.B. Inhibitory effect of thiosemicarbazone derivatives on Junin virus replication in vitro. Antivir. Chem. Chemother. 2003, 14, 99–105. [Google Scholar] [CrossRef]
- Coşkun, G.P.; Djikic, T.; Hayal, T.B.; Türkel, N.; Yelekçi, K.; Şahin, F.; Küçükgüzel, Ş.G. Synthesis, molecular docking and anticancer activity of diflunisal derivatives as cyclooxygenase enzyme inhibitors. Molecules 2018, 23, 1969. [Google Scholar] [CrossRef]
- Kaproń, B.; Czarnomysy, R.; Paneth, A.; Wujec, M.; Bielawski, K.; Bielawska, A.; Swiątek, Ł.; Rajtar, B.; Polz-Dacewicz, B.; Plech, T. Dual antibacterial and anticancer activity of 4-benzoyl-1-dichlorobenzoylthiosemicarbazide derivatives. Anti-Cancer Agents Med. Chem. 2018, 18, 529–540. [Google Scholar] [CrossRef]
- Prashanthi, M.; Babu, H.R.; Rani, J.U. Design, Synthesis and Molecular Docking Studies of Novel Indole–Isoxazole–Triazole Conjugates as Potent Antibacterial Agents. Russ. J. Bioorg. Chem. 2021, 47, 601–608. [Google Scholar] [CrossRef]
- Rimpiläinen, T.; Nunes, A.; Calado, R.; Fernandes, A.S.; Andrade, J.; Ntungwe, E.; Spengler, G.; Szemerédi, N.; Rodrigues, J.; Gomes, J.P.; et al. Increased Antibacterial Properties of Indoline-Derived Phenolic Mannich Bases. Eur. J. Med. Chem. 2021, 220, 113459. [Google Scholar] [CrossRef]
- Yang, G.; Shi, L.; Pan, Z.; Wu, L.; Fan, L.; Wang, C.; Xu, C.; Liang, J. The Synthesis of Coumarin Thiazoles Containing a Trifluoromethyl Group and Their Antifungal Activities. Arab. J. Chem. 2021, 14, 102880. [Google Scholar] [CrossRef]
- Antiqueira-Santos, P.; Teixeira, W.K.O.; Flores, A.F.C.; Piovesan, L.A.; Nery, L.E.M.; Votto, A.P. de S. Synthesis of Pyrazoline Fatty Chain Derivatives and Its Effects on Melanoma Cells. Bioorg. Med. Chem. Lett. 2021, 41, 127988. [Google Scholar] [CrossRef]
- Jung, Y.H.; Jain, S.; Gopinatth, V.; Phung, N.B.; Gao, Z.G.; Jacobson, K.A. Structure Activity Relationship of 3-Nitro-2-(Trifluoromethyl)-2H-Chromene Derivatives as P2Y6 Receptor Antagonists. Bioorg. Med. Chem. Lett. 2021, 41, 128008. [Google Scholar] [CrossRef]
- Krátký, M.; Svrčková, K.; Vu, Q.A.; Štěpánková, Š.; Vinšová, J. Hydrazones of 4-(Trifluoromethyl)Benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase. Molecules 2021, 26, 989. [Google Scholar] [CrossRef]
- Shah, P.; Westwell, A.D. The role of fluorine in medicinal chemistry. J. Enzym. Inhib. Med. Chem. 2007, 22, 527–540. [Google Scholar] [CrossRef]
- Janowska, S.; Khylyuk, D.; Andrzejczuk, S.; Wujec, M. Design, Synthesis, Antibacterial Evaluations and In Silico Studies of Novel Thiosemicarbazides and 1,3,4-Thiadiazoles. Molecules 2022, 27, 3161. [Google Scholar] [CrossRef]
- Plech, T.; Wujec, M.; Siwek, A.; Kosikowska, U.; Malm, A. Synthesis and antimicrobial activity of thiosemicarbazides, s-triazoles and their Mannich bases bearing 3-chlorophenyl moiety. Eur. J. Med. Chem. 2011, 46, 241–248. [Google Scholar] [CrossRef]
- Janowska, S.; Stefańska, J.; Khylyuk, D.; Wujec, M. The Importance of Substituent Position for Antibacterial Activity in the Group of Thiosemicarbazide Derivatives. Molecules 2024, 29, 1333. [Google Scholar] [CrossRef]
- Power Analysis and Sample Size Software. NCSS, LLC.: Kaysville, UT, USA, 2015; Available online: https://www.ncss.com/software/pass/ (accessed on 20 October 2022).
- Tejchman, W.; Kołodziej, P.; Kalinowska-Tłuścik, J.; Nitek, W.; Żuchowski, G.; Bogucka-Kocka, A.; Żesławska, E. Discovery of Cinnamylidene Derivative of Rhodanine with High Anthelmintic Activity against Rhabditis sp. Molecules 2022, 27, 2155. [Google Scholar] [CrossRef]
- Dziduch, K.; Kołodziej, P.; Paneth, A.; Bogucka-Kocka, A.; Wujec, M. Synthesis and Anthelmintic Activity of New Thiosemicarbazide Derivatives—A Preliminary Study. Molecules 2020, 25, 2770. [Google Scholar] [CrossRef]
- Boucher, H.W.; Talbot, G.H.; Bradley, J.S.; Edwards, J.E.; Gilbert, D.; Rice, L.B.; Scheld, M.; Spellberg, B.; Bartlett, J. Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clin. Infect. Dis. 2009, 48, 1–12. [Google Scholar] [CrossRef]
- Kolendi, C.L. Methicillin-Resistant Staphylococcus aureus (MRSA): Etiology, At-Risk Populations and Treatment; Nova Science Publishers Inc.: New York, NY, USA, 2010. [Google Scholar]
- Que, Y.A.; Haefliger, J.A.; Piroth, L.; François, P.; Widmer, E.; Entenza, J.M.; Sinha, B.; Herrmann, M.; Francioli, P.; Vaudaux, P.; et al. Fibrinogen and Fibronectin Binding Cooperate for Valve Infection and Invasion in Staphylococcus aureus Experimental Endocarditis. J. Exp. Med. 2005, 16, 201. [Google Scholar] [CrossRef]
- Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.D.; Mazur, M.; Telser, J. Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. Int. J. Biochem. Cell Biol. 2007, 39, 44–84. [Google Scholar] [CrossRef]
- Zhao, W.; Diz, D.I.; Robbins, M.E. Oxidative Damage Pathways in Relation to Normal Tissue Injury. Br. J. Radiol. 2007, 80, 23–31. [Google Scholar] [CrossRef]
- Aruoma, O.I. Free Radicals, Oxidative Stress, and Antioxidants in Human Health and Disease. J. Am. Oil Chem. Soc. 1998, 75, 199–212. [Google Scholar] [CrossRef]
- Devasagayam, T.P.; Tilak, J.C.; Boloor, K.K.; Sane, K.S.; Ghaskadbi, S.S.; Lele, R.D. Free Radicals and Antioxidants in Human Health: Current Status and Future Prospects. J. Assoc. Physicians India 2004, 52, 794–804. [Google Scholar]
- Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free Radicals, Antioxidants and Functional Foods: Impact on Human Health. Pharmacogn. Rev. 2010, 4, 118–126. [Google Scholar] [CrossRef]
- Marengo, B.; Nitti, M.; Furfao, A.L.; Colla, R.; de Cucis, C.; Marinari, U.M.; Pronzato, M.A.; Traverso, N.; Domenicotti, C. Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy. Oxid. Med. Cell Longev. 2016, 2016, 6235641. [Google Scholar] [CrossRef]
- Ali, S.S.; Ahsan, H.; Zia, M.K.; Siddiqui, T.; Khan, F.H. Understanding oxidants and antioxidants: Classical team with new players. J. Food Biochem. 2020, 44, e13145. [Google Scholar] [CrossRef]
- Garcia, Y.J.; Rodriguez-Malaver, A.J.; Penaloza, N. Lipid peroxidation measurement by thiobarbituric acid assay in rat cerebellar slices. J. Neurosci. Methods 2005, 144, 127–135. [Google Scholar] [CrossRef]
- Zhao, M.J.; Yuan, S.; Zi, H.; Gu, J.M.; Fang, C.; Zeng, X.T. Oxidative Stress Links Aging-Associated Cardiovascular Diseases and Prostatic Diseases. Oxid. Med. Cell Longev. 2021, 2021, 5896136. [Google Scholar] [CrossRef]
- Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Morte, D.D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bonaduce, D.; et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging 2018, 13, 757–772. [Google Scholar] [CrossRef]
- Serra, J.A.; Domínguez, R.O.; Marschoff, E.R.; Guareschi, E.M.; Famulari, A.L.; Boveris, A. Systemic Oxidative Stress Associated with the Neurological Diseases of Aging. Neurochem. Res. 2009, 34, 2122–2132. [Google Scholar] [CrossRef]
- Barrera, G.; Pizzimenti, S.; Daga, M.; Dianzani, C.; Arcaro, A.; Cetrangolo, G.P.; Giordano, G.; Cucci, M.A.; Graf, M.; Gentile, F. Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders. Antioxidants 2018, 7, 102. [Google Scholar] [CrossRef]
- Spickett, C.M. The Lipid Peroxidation Product 4-Hydroxy-2-Nonenal: Advances in Chemistry and Analysis. Redox Biol. 2013, 1, 145–152. [Google Scholar] [CrossRef]
- Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction. Anal. Biochem. 1979, 95, 351–358. [Google Scholar] [CrossRef]
- Chen, J.; Yang, J.; Ma, L.; Li, J.; Shahzad, N.; Kim, C.K. Structure-Antioxidant Activity Relationship of Methoxy, Phenolic Hydroxyl, and Carboxylic Acid Groups of Phenolic Acids. Sci. Rep. 2020, 10, 2611. [Google Scholar] [CrossRef]
- Mazzone, G.; Malaj, N.; Galano, A.; Russo, N.; Toscano, N. Antioxidant Properties of Several Coumarin–Chalcone Hybrids from Theoretical Insights. RSC Adv. 2015, 5, 565–575. [Google Scholar] [CrossRef]
- Gulcin, I. Antioxidant and Antiradical Activities of L-carnitine. Life Sci. 2006, 78, 803–811. [Google Scholar] [CrossRef]
- Spiegel, M.; Kapusta, K.; Kołodziejczyk, W.; Saloni, J.; Żbikowska, B.; Hill, G.A.; Sroka, Z. Antioxidant Activity of Selected Phenolic Acids-Ferric Reducing Antioxidant Power Assay and QSAR Analysis of the Structural Features. Molecules 2020, 25, 3088. [Google Scholar] [CrossRef]
- Castelluccio, C.; Paganga, G.; Melikian, N.; Bolwell, G.P.; Pridham, J.; Sampson, J.; Rice-Evans, C. Antioxidant Potential of Intermediates in Phenylpropanoid Metabolism in Higher Plants. FEBS Lett. 1995, 368, 188–192. [Google Scholar] [CrossRef]
- Razzaghi-Asl, N.; Garrido, J.; Khazraei, H.; Borges, F.; Firuzi, O. Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure-Activity Relationships. Curr. Med. Chem. 2013, 20, 4436–4450. [Google Scholar] [CrossRef]
- Rimal, I.; Reddy, P.S.; Chavali, M. Halogen Substituted Chalcone as Potential Antioxidants: An In Vitro Study. Adv. Sci. Eng. Med. 2012, 4, 499–504. [Google Scholar]
- Olajide, T.M.; Liu, T.; Liu, H.; Weng, X. Antioxidant Properties of Two Novel Lipophilic Derivatives of Hydroxytyrosol. Food Chem. 2020, 315, 126197. [Google Scholar] [CrossRef]
- PL 232918 B1; Method for the Culture of Nematodes of Rhabditis sp. Genus and Determination of the Nematocidal Substances Activity. Uniwersytet Medyczny w Lublinie PL: Warsaw, Poland, 2019.
- The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 12.0, 2022. Ecast: EUCAST. Available online: https://www.eucast.org/ (accessed on 2 February 2023).
- O’Donnell, F.; Smyth, T.J.P.; Ramachandran, V.N.; Smyth, W.F. A Study of the Antimicrobial Activity of Selected Synthetic and Naturally Occurring Quinolines. Int. J. Antimicrob. Agents 2010, 35, 30–38. [Google Scholar] [CrossRef]
- Wiegand, I.; Hilpert, K.; Hancock, R.E.W. Agar and Broth Dilution Methods to Determine the Minimal Inhibitory Concentration (MIC) of Antimicrobial Substances. Nat. Protoc. 2008, 3, 163–175. [Google Scholar] [CrossRef]
- Kubiak-Tomaszewska, G. Effect of Hydroxyl Groups Esterification with Fatty Acids on the Cytotoxicity and Antioxidant Activity of Flavones. Molecules 2022, 27, 420. [Google Scholar] [CrossRef]
- Chawla, R.; Arora, R.; Kumar, R.; Sharma, A.; Prasad, J.; Singh, S.; Sagar, R.; Chaudhary, P.; Shukla, S.; Kaur, G.; et al. Antioxidant Activity of Fractionated Extracts of Rhizomes of High-altitude Podophyllum hexandrum: Role in Radiation Protection. Mol. Cell Biochem. 2005, 273, 193–208. [Google Scholar] [CrossRef]
- Ghani, M.A.; Barril, C.; Bedgood, D.R., Jr.; Prenzler, P.D. Measurement of Antioxidant Activity with the Thiobarbituric Acid Reactive Substances Assay. Food Chem. 2017, 230, 195–207. [Google Scholar] [CrossRef]
- Christodoulou, M.C.; Orellana Palacios, J.C.; Hesami, G.; Jafarzadeh, S.; Lorenzo, J.M.; Domínguez, R.; Moreno, A.; Hadidi, M. Spectrophotometric Methods for Measurement of Antioxidant Activity in Food and Pharmaceuticals. Antioxidants 2022, 11, 2213. [Google Scholar] [CrossRef]
- de Zwart, L.L.; Meerman, J.H.; Commandeur, J.N.; Vermeulen, N.P. Biomarkers of Free Radical Damage Applications in Experimental Animals and In Humans. Free Radic. Biol. Med. 1999, 26, 202–226. [Google Scholar] [CrossRef]
- Hou, Y.; Carne, A.; McConnell, M.; Bekhit, A.A.; Mros, S.; Amagase, K.; Bekhit, A.E.A. In Vitro Antioxidant and Antimicrobial Activities, and In Vivo Anti-inflammatory Activity of Crude and Fractionated PHNQs From Sea Urchin (Evechinus chloroticus). Food Chem. 2020, 316, 126339. [Google Scholar] [CrossRef]
- Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Adv. Drug Deliver. Rev. 2001, 46, 3–26. [Google Scholar] [CrossRef]
- Ertl, P.; Rohde, B.; Selzer, P. 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. 2000, 43, 3714–3717. [Google Scholar] [CrossRef]
- Veber, D.F.; Johnson, S.R.; Cheng, H.-Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates. J. Med. Chem. 2002, 45, 2615–2623. [Google Scholar] [CrossRef]
Compound | Antituberculosis | Antibacterial | Antiparasitic |
---|---|---|---|
3a | 0.551 | 0.381 | 0.441 |
3b | 0.513 | 0.337 | 0.341 |
3c | 0.479 | 0.440 | 0.390 |
3d | 0.555 | 0.389 | 0.328 |
3e | 0.541 | 0.363 | 0.269 |
3f | 0.594 | 0.414 | 0.335 |
Compounds | Staphylococcus aureus ATCC 25923 | Staphylococcus aureus ATCC 29213 | Staphylococcus aureus ATCC 6538 | Staphylococcus aureus ATCC 43300 | Staphylococcus epidermidis ATCC 12228 | Micrococcus luteus ATCC 10240 | Bacillus cereus ATCC 10876 | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | |
3a | 1.95 | 1000 | 1.95 | 1000 | 1.95 | 1000 | 3.9 | 1000 | 1.95 | 15.63 | 1.95 | 15.63 | 1.95 | 15.63 |
3b | 62.5 | nd * | >1000 | nd * | >1000 | nd * | ->1000 | nd * | >1000 | nd * | 500 | nd * | >1000 | nd * |
3c | 250 | nd * | >1000 | nd * | ->1000 | nd * | ->1000 | nd * | 1000 | nd * | 1000 | nd * | >1000 | nd * |
3d | 1000 | nd * | >1000 | nd * | ->1000 | nd * | ->1000 | nd * | 1000 | nd * | 1000 | nd * | >1000 | nd * |
3e | 31.25 | >1000 | 15.63 | >1000 | 15.63 | >1000 | 31.25 | >1000 | 31.25 | >1000 | 15.63 | >1000 | 7.81 | >1000 |
3f | 62.5 | nd * | >1000 | nd * | >1000 | nd * | >1000 | nd * | 1000 | nd * | 1000 | nd * | >1000 | nd * |
4 | 1000 | nd * | >1000 | nd * | >1000 | nd * | >1000 | nd * | 500 | nd * | 1000 | nd * | >1000 | nd * |
1 Cef | 0.49 | nt | 0.98 | nt | 0.25 | 0.25 | 31.25 | |||||||
2 Van | 2 | 2 | 2 | 2 |
Cancer Cells | Normal Cells | ||
---|---|---|---|
SW 620 d | V 79 e | ||
Compound | IC50 b | SI c | IC50 b |
3a | 69.02 ± 12.63 | 0.59 | 40.49 ± 3.83 |
3b | >100 | 1 | >100 |
3c | >100 | 1 | >100 |
3d | >100 | 0.69 | 69.09 ± 5.45 |
3e | 89.87 ± 14.61 | 1.06 | >100 |
3f | >100 | 1 | >100 |
4 | >100 | 1 | >100 |
Ref f | 1.83 ± 0.10 | 0.16 | 0.46 ± 0.03 |
Compound | MDA [mM × 10−3] | Antioxidative Potential Value [%] |
---|---|---|
3a | 1.395 ± 0.232 * | 48.3 |
3b | 1.703 ± 0.177 ** | 36.9 |
3c | 1.773 ± 0.077 *** | 34.3 |
3d | 1.320 ± 0.143 ** | 51.1 |
3e | 1.274 ± 0.121 ** | 52.8 |
3f | 1.450 ± 0.006 *** | 46.3 |
4 | 2.022 ± 0.121 ** | 25.1 |
Control Sample | 2.699 ± 0.088 | 0.0 |
Compound | Lipinski’s Parameters | |||||
---|---|---|---|---|---|---|
TPSA | Hydrogen Bond Acceptor | Hydrogen Bond Donor | log p | Mass | Rotatable Bonds (No’s) | |
3a | 53.15 | 4 | 3 | 3.67 | 373.79 | 6 |
3b | 62.39 | 5 | 3 | 3.05 | 369.37 | 7 |
3c | 53.15 | 4 | 3 | 3.39 | 319.35 | 8 |
3d | 53.15 | 4 | 3 | 3.44 | 353.37 | 6 |
3e | 53.15 | 4 | 3 | 3.15 | 357.33 | 6 |
3f | 53.15 | 4 | 3 | 3.01 | 339.34 | 6 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lasek, P.; Kosikowska, U.; Kołodziej, P.; Kubiak-Tomaszewska, G.; Krzyżanowska, N.; Szostek, T.; Struga, M.; Feldo, M.; Bogucka-Kocka, A.; Wujec, M. New Thiosemicarbazide Derivatives with Multidirectional Biological Action. Molecules 2024, 29, 1529. https://doi.org/10.3390/molecules29071529
Lasek P, Kosikowska U, Kołodziej P, Kubiak-Tomaszewska G, Krzyżanowska N, Szostek T, Struga M, Feldo M, Bogucka-Kocka A, Wujec M. New Thiosemicarbazide Derivatives with Multidirectional Biological Action. Molecules. 2024; 29(7):1529. https://doi.org/10.3390/molecules29071529
Chicago/Turabian StyleLasek, Patryk, Urszula Kosikowska, Przemysław Kołodziej, Grażyna Kubiak-Tomaszewska, Natalia Krzyżanowska, Tomasz Szostek, Marta Struga, Marcin Feldo, Anna Bogucka-Kocka, and Monika Wujec. 2024. "New Thiosemicarbazide Derivatives with Multidirectional Biological Action" Molecules 29, no. 7: 1529. https://doi.org/10.3390/molecules29071529
APA StyleLasek, P., Kosikowska, U., Kołodziej, P., Kubiak-Tomaszewska, G., Krzyżanowska, N., Szostek, T., Struga, M., Feldo, M., Bogucka-Kocka, A., & Wujec, M. (2024). New Thiosemicarbazide Derivatives with Multidirectional Biological Action. Molecules, 29(7), 1529. https://doi.org/10.3390/molecules29071529