Synthesis, characterization and antimicrobial activity of some novel 4-amino-5- phenyl-4H-1,2,4-triazole-3-thiol derivatives

Year 2023, , 294 - 301, 28.12.2023

Nurhan Gümrükçüoğlu , Muhammad Imran , Inam Iqbal

https://doi.org/10.26650/IstanbulJPharm.2023.1301086

Abstract

Background and aims: The discovery of new antifungals and antimicrobials to overcome resistance has always been a crucial topic for sustainable world health. Since sulfur-containing triazole heterocycles derivatives have shown greater interest due to their valuable applications, we reported herein, the synthesis of some mercaptotriazole derivatives to discover underlying structural requirements for antimicrobial and antifungal activity.

Methods: Firstly, the benzoic acid hydrazide was synthesized. Then it was reacted with carbon disulfide in the solution of alkali ethanol to give potassium dithiocarbazinate salt. Then the basic nucleus 4-amino-5-phenyl-1-4H-1,2,4-triazole-3-thiol was prepared by cyclization of potassium salt with hydrazine hydrate. After that, a condensation reaction with different aldehydes was conducted to synthesize Schiff bases, which were cyclized by treating with thioglycolic acid to prepare desired compounds.

Results: All the synthesized compounds were confirmed by their melting point, FTIR, 1H-NMR, and 13C-NMR spectra, elemental analysis was determined for their antimicrobial activity by using a simple susceptibility screening test with agar-well diffusion. Few compounds showed promising activity against bacteria and yeast-like fungi.

Conclusion: 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol derivatives proved promising antimicrobial activities.

Keywords

Triazole-3-thiol, antimicrobial activity, Schiff base, thiazolidenon derivative, triflucan

References

• Ahmed, A., Majeed, I.Y., Asaad, N., Ahmed, R.M., Kamil, G.M., & Rahman, S.S. (2022). Some 3,4,5-Trisubstituted-1,2,4-triazole Synthesis, Antimicrobial Activity, and Molecular Dock-ing Studies. Egyption Journal of Chemistry, 65(3):395-401. https://dx.doi.org/10.21608/ejchem.2021.93025.4397 google scholar
• Bakr, F., Abdel-Wahab, M.S., Bekheit, H.M., Mashaly, A.A., & Fahmy, H.M. (2023). Novel Dinitrophenylhydrazones Contain-ing 1,2,3-Triazole Nucleus as Disperse Dyes for Polyester Fab-ric Dyeing and Functional Finishing and Antibacterial Ac-tivities. Polycyclic Aromatic Compounds, 43(4): 3342-3352. https://doi.org/10.1080/10406638.2022.2068623 google scholar
• Benhammadi, S., Salimairaten, S., & Othman, A. (2016). Synthetic studies and antibacterial activity of nucleobases and their N-and S-glucosides from 2-amino benzoic acid and its benzamido derivatives. Oriental Journal of Chemistry, 32(5):2567-2576. http://dx.doi.org/10.13005/ojc/320528 google scholar
• Blank, B., Nichols, D.M., & Vaidya, P.D. (1972). Synthesis of 1,2,4-triazoles as potential hypoglycemic agents. Journal of Medicinal Chemistry, 15(6):694-696. https://doi.org/10.1021/jm00276a040 google scholar
• Cacic, M., Molnar, M., Sarkanj, B., Has-Schön, E., & Rajkovic, V. (2010). Synthesis and biological evaluation of some Schiff bases of [4-(amino) -5- phenyl- 4H-1, 2, 4-triazole- 3- thiol]. Molecules, 6795-6809. google scholar
• Cavusoglu, B., Yurttas, L., & Canturk, Z. (2018). The synthesis, anti-fungal and apoptotic effects of triazole-oxadiazoles against Can-dida species. European Journal of Medicinal Chemistry, 144: 255-261. https://doi.org/10.1016/j.ejmech.2017.12.020 google scholar
• Demirbas, N., Ugurluoglu, R., & Demirbas, A. (2002) Syn-thesis of 3-Alkyl(Aryl)-4-alkylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones and 3-Alkyl-4-alkylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones as Antitumor Agents. Bioorganic & Medic-inal Chemistry, 10:3717-3723. https://doi.org/10.1016/s0968-0896(02)00420-0 google scholar
• Desai, S.P., Momin, Y.H., Taralekar, S.T., Dange, Y.D., Jagtap, S.R. & Khade, H.P. (2021). Evaluation of potential in vitro anticancer and antimicrobial activities of synthesized 5-mercapto-4-substituted 1,2,4 triazole derivatives. Annals of Phytomedicine, 10(2): 273279. http://dx.doi.org/10.21276/ap.2021.10.2.36 google scholar
• Diogo, A.N., Bertrand, B., Thorimbert, S., Gontard, G., Kahn, S.N., Echeverri, A., & Contreras-Garrfa, J. (2023). 3-Hydroxypyridinyl-Substituted-1,2,4-Triazoles as New ESIPT Based Fluorescent Dyes: Synthesis and Structure-Fluorescence Properties Correlations. Advanced Optical Materials, 11:1-12. https://doi.org/10.1002/adom.202300336 google scholar
• ElBelghiti, M., Karzazi, Y., Dafali, A., Hammouti, B., Bentiss, F., Obot, I.B., Bahadur, I., & Ebenso, E.E. (2016). Experimen-tal, quantum chemical and Monte Carlo simulation studies of 3,5-disubstituted-4-amino-1,2,4-triazoles as corrosion inhibitors on mild steel in acidic medium. Journal of Molecular Liquids, 218:281-293. http://dx.doi.org/10.1016/j.molliq.2016.01.076 google scholar
• El-Essawy, F.A., El-Sayed, W.A., El-Kafrawy, S.A., Morshedy, A.S., & Abdel-Rahman, A.H.Z. (2008). Anti-hepatitis B virus activity of new 1,2,4-triazol-2- yl- and 1,3,4-oxadiazol-2-yl-2-pyridinone derivatives. Zeitschrift für Naturforschung C, 63:667-772. PMID:19040105 google scholar
• Fedotov, S.O., & Hotsulia, A.S. (2023). Synthesis and proper-ties of S-alkyl 4-amino-5-(5-(3-fluorophenyl)-pyrazol-3-yl)-1,2,4-triazole-3-thiol derivatives. Pharmacy and Medicine: Sci-ence and Practice, 16(1): 5-11. https://doi.org/10.14739/2409-2932.2023.1.273461 google scholar
• Fidler, D.P (1998). Legal Issues Associated with Antimicrobial Drug Resistance. Emerging Infectious Diseases, 4(2):169-177. https://doi.org/10.3201/eid0402.980204 google scholar
• Howatt, K.A. (2005). Carfentrazone ethyl injury to spring wheat (Triticum aestivum) is minimized by some ALS2 inhibiting herbicides 1. Weed Technology, 19: 777-783. http://dx.doi.org/10.1614/WT-04-206.1 google scholar
• Huntsman, E. & Balsells, J. (2005). New Method for the General Synthesis of [1,2,4]Triazolo[1,5-a]pyridines. European Journal of Organic Chemistry, 3761-3765. https://doi.org/10.1002/ejoc.200500247 google scholar
• Kane, J.M., Dudley, M.W., Sorensen, S.M., & Miller, F.P. (1988). 2,4-Dihydro-3H-1,2,4-triazole-3-thiones as Potential Antidepres-sant Agents. Jounal of Medicinal Chemistry, 31(6):1253-1258. https://doi.org/10.1002/chin.198843203 google scholar
• Karabasanagouda, T., Adhikari, A.V., & Shetty, N.S. (2006). Synthesis and antimicrobial activities of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines carrying thioalkyl and sulphonyl phenoxy moi-eties. European Journal of Medicinal Chemistry, 42(4):521-529. https://doi.org/10.1016/j.ejmech.2006.10.010 google scholar
• Karpun, Ye., & Polishchuk, N. (2021). Synthesis and antimi-crobial activity of s-substituted derivatives of 1,2,4-triazol-3-thiol. ScienceRise: Pharmaceutical Science, 3(31): 64-69. doi: http://doi.org/10.15587/2519-4852.2021.235976 google scholar
• Kazeminejad, Z., Marzi M., Shiroudi, A., Kouhpayeh, S.A., Farjam, M., & Zarenezhad, E. (2022). Novel 1, 2, 4-Triazoles as Anti-fungal Agents. BioMed Research International, 4584846, 1-39. https://doi.org/10.1155/2022/4584846 google scholar
• Klimesova, V., Zahajska, L., Waisser, K., Kaustova, J., & Moll-mann, U. (2004). Synthesis and antimycobacterial activity of 1,2,4-triazole-3-benzylsulfanyl derivatives. Il Farmaco, 59:279-288. https://doi.org/10.1016/j.farmac.2004.01.006 google scholar
• Koparir, P., Parlak, A.E., Karatepe, A., & Omar, R.A. (2022). Elucida-tion of potential anticancer, antioxidant and antimicrobial proper-ties of some new triazole compounds bearing pyridine-4-yl moi-ety and cyclobutane ring. Arabian Journal of Chemistry, 15:1-10. https://doi.org/10.1016/j.arabjc.2022.103957 google scholar
• Kumari, M., Tahlan, S., Narasimhan, B., Ramasamy, K., Meng, S., Shah, S.A.A., Mani, V., & Kakkar, S. (2021). Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents. BMC Chemistry, 15(5):1-16. https://doi.org/10.1186/s13065-020-00717-y google scholar
• Küçükgüzel, I., Güniz, S.K., Rollas, S., Otük-Saniş, G., Ozdemir, O., Bayrak, I., Altuğ, T., & Stables, J.P. (2004). Synthesis of some 3-(arylalkylthio)-4-alkyl/aryl-5-(4-aminophenyl)-4H-1,2,4-triazole derivatives and their anticonvulsant activity. Il Farmaco, 59(11):893-901. https://doi.org/10.1016/j.farmac.2004.07.005. google scholar
• Li, D., He, M., Chen, B., & Hu, B. (2019). Mag-netic porous organic polymers for magnetic solid-phase extraction of triazole fungicides in vegetables prior to their determination by gas chromatography-flame ioniza-tion detection. Journal of Chromatography A, 1601: 1-8. https://doi.org/10.1016/j.chroma.2019.04.062 google scholar
• Li, N., Guan, Q., Hong, Y., Zhang, B., Li, M., Li, X., Li, B., Wu, L. & Zhang, W. (2023). Discovery of 6-aryl-2-(3,4,5-trimethoxyphenyl)thiazole[3,2-b][1,2,4] triazoles as potent tubulin polymerization inhibitors. European Journal of Medicinal Chemistry, 56:1-13.https://doi.org/10.1016/j.ejmech.2023.115402 google scholar
• Liu, G., Tian, M., Lu, M., Shi, W., Li, L., Gao, Y., Li, T., & Xu, D. (2021). Preparation of magnetic MOFs for use as a solid-phase extraction absorbent for rapid adsorption of triazole pesticide residues in fruits juices and vegetables. Journal of Chromatography B 1166:122500. https://doi.org/10.1016/j.jchromb.2020.122500 google scholar
• Ma, Q.-C., Yue, T.-C., Cao, Q.-W., Xie, Z.-B., Dong, Q.-W., & Wang, D.-Z. (2023). Study on magnetic and dye adsorption properties of five coordination polymers based on triazole car-boxylic acid ligands. Journal of Molecular Structure, 1284:1-9. https://doi.org/10.1016/j.molstruc.2023.135379 google scholar
• Mohamed, N.G., Sheha, M.M., Hassan, H.Y., Abdel-Hafez, L.J.M., & Omar, F.A. (2018). Synthesis, antimicrobial activity and molecular modeling study of 3-(5-amino-(2H)-1, 2, 4-triazol-3-yl]-naphthyridinones as potential google scholar
• DNA-gyrase inhibitors. Bioorganic Chemistry, 81: 599-611. https://doi.org/10.1016/j.bioorg.2018.08.031 google scholar
• Mullican, M.D., Wilson, M.W., Conner, D.T., Kostlan, C.R., Schrier, D.J., & Dyer, R.D. (1993). Design of 5-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,3,4-thiadiazoles,-1,3,4-oxadiazoles and -1,2,4-triazoles as orally active, nonulcerogenic antiinflammatory agents. Journal of Medicinal Chemistry, 36(8):1090-1099. https://doi.org/10.1021/jm00060a017 google scholar
• Nazarov, V., Miroshnichenko, D., Ivakh, O., & Pyshyev, S. (2023). State of the Art in Industrial Application of Amino-1,2,4-Triazoles. Mini-Reviews in Organic Chemistry, 20(4):394-402. http://dx.doi.org/10.2174/1570193X19666220331155015 google scholar
• Popiolek, L., Paruch, K., Patrejko, P., Biernasiuk, A., & Wujec, M. (2016). New 3-hydroxy-2-naphthoic hydrazide derivatives: thiosemicarbazides and 1,2,4-triazole-3-thiones, their synthesis and in vitro antimicrobial evaluation. Journal ofthe Iranian Chem-ical Society, 13:1945-1951. http://dx.doi.org/10.1007/s13738-016-0911-1 google scholar
• Popova, L., Ivanchenko, O., Njanikova, G., Vershilov, S., Suchilova, V., & Gaurav, B. (2021). Perfluorosubstituted Derivatives of 1,3-Diazine and 1,2,4-Triazole as a Means of Protecting Industrial Structures from Microbiologically Induced Corrosion. In: Vatin, N., Borodinecs, A., Teltayev, B. (eds) Proceedings of EECE 2020. EECE 2020. Lecture Notes in Civil Engineering, vol 150. Springer, Cham. https://doi.org/10.1007/978-3-030-72404-7_5 google scholar
• Sameliuk, Y.G., Zedan, F.A., & Kaplaushenko, T.M. (2021). 1,2,4-Triazole Derivatives In Medicine And Pharmacy And Application Prospects. Journal of Faculty of Pharmacy of Ankara University, 45(3): 598-614. htps://doi.org/10.33483/jfpau.885888 google scholar
• Seebunrueng, K., Tamuang, S., Ruangchai, S., Sansuk, S., & Sri-jaranai, S. (2021). In situ self-assembled coating of surfactant-mixed metal hydroxide on Fe3 O4 @SiO2 magnetic composite for dispersive solid phase micro extraction prior to HPLC analy-sis of triazole fungicides. Microchemical Journal, 168: 106396 https://doi.org/10.1016/j.microc.2021.106396 google scholar
• Sekhar, M.M., Nagarjuna, U., Padmavathi, V., Padmaja, A., Vasudeva, N.R., & Vijaya, T. (2018). Synthesis and antimicrobial activity of pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. European Journal of Medicinal Chemistry, 145:1-10. https://doi.org/10.1016/j.ejmech.2017.12.067 google scholar
• Selvaraj, J., Pranabesh, S., Shanish, A., Rajagopal, K., Byran, G., Subramanian, G., & Kannan, E. (2011). Synthesis And Biolog-ical Evaluaiıon of Some Schiff Bases of [4-(Amino)-5- Phenyl-4h-1,2,4-Trıazole-3-Thıol]Ring terming Polymerisation, Part-B-1. google scholar
• Pakistan Journal of Pharmaceutical Sciences, 24(2):109-112. google scholar
• Shah, M.H., Mhasalkar, M.Y., Patki, V.M., Deliwala, C.V., & Sheth, U.K. (1969). New 1,2,4(H)-Triazole Derivatives as Di-uretic Agents. Journal of Pharmaceutical Sciences, 58(2):1399. https://doi.org/10.1002/jps.2600581123 google scholar
• Shang, J., Wang, W.M., Li, Y.H., Song, H.B., Li, Z.M., & Wang, J.G. (2012). Synthesis, crystal structure, in vitro acetohydroxyacid synthase inhibition, in vivo herbicidal activity, and 3D-QSAR of new asymmetric aryl disulfides. Jounal of Agricultural and Food Chemistry, 29(34):8286-8293. https://doi.org/10.1021/jf302206x google scholar
• Shcherbyna, R., Pruhlo, Y., Duchenko, M., Kulagina, M., Kudria, V., & Vashchuk Valentyna, V. (2022). Evaluation of Antioxi-dant Activity of 1,2,4-Triazole Derivatives With Morpholine Moi-ety. Hacettepe University Journal of the Faculty of Pharmacy, 42(2):73-82. https://doi.org/10.52794/hujpharm.1033112 google scholar
• Shevtsov, D.S., Shikhaliev, Kh.S., Stolpovskaya, N.W., Kruzhilin, A.A., Potapov, A.Yu., Zartsyn, I.D., Kozaderov, O.A., Lyapun, D.V., Prabhakar, C., & Tripathi, A. (2020). 3-Alkyl-5-amino-1,2,4-triazoles synthesized from the fatty acids of sunflower oil processing waste as corrosion inhibitors for copper in chloride en-vironments. International Journal of Corrosion and Scale Inhibi-tion, 9(2):726-744. https://dx.doi.org/10.17675/2305-6894-2020-9-2-21 google scholar
• Shimada, Y., Ito, T., Maeta, H., Matsuoka, K. & Sato, K. (2006). A Novel Heterocyclic Cyan Dyeforming Coupler for Color Photo-graphic Use: Synthesis of 1H-Pyrrolo [ 1,2-b] [1, 2, 4]triazole. Journal of Synthetic Organic Chemistry, 64(3): 222-226. google scholar
• Sloop, J. (2023). Synthesis of Heteroaromatic Compounds. Molecules, 28:1-4. https://doi.org/10.3390/molecules28083563 google scholar
• Sobhi, M.G., Mastoura, M.E., Zeinab, A.M., Nabila, A.K., Sraa, A.M. & Amirah, M.S. (2022) Synthesis, Characterization, and An-timicrobial Evaluation of Some New 1,4-Dihydropyridines-1,2,4-Triazole Hybrid Compounds. Polycyclic Aromatic Compounds, 42(1):173-185. https://doi.org/10.1080/10406638.2020.1720751 google scholar
• Subhas, S., Sindhu, K.N., & Sreeveena, K. (2019). The Signifi-cance of 1, 2, 4 Triazoles in Agriculture Science: A Review Re-search Journal of Pharmacy and Technology, 12(10):5091- 5071. http://dx.doi.org/10.5958/0974-360X.2019.00882.5 google scholar
• Sztanke, K., Pasternak, K., Rzymowska, J., Sztanke, M., & Kandefer-Szerszen, M. (2008). Synthesis, structure elucidation and identi-fication of antitumoural properties of novel fused 1,2,4-triazine aryl derivatives. European Journal of Medicinal Chemistry, 43(5):1085-1094. https://doi.org/10.1016/j.ejmech.2007.07.009 google scholar
• Tozkoparan, B., Kupeli, E., Ozalp, S., & Ertan, M. (2005). Synthe-sis and evaluation of analgesic/antiinflammatory and antimicro-bial activities of 3-substituted-1,2,4-triazole-5- thiones. Arzneim-Forsch/Drug Research, 55(9): 533-540. https://doi.org/10.1055/s-0031-1296901 google scholar
• Tkach, V.V, Kushnir, M.V., Oliveira, S.C., Shevchenko, I.M., Odyntsova, V.M., Omelyanchik, V.M.... Vaz dos Reis, L. google scholar
• (2023). Theoretical Description for Anti-COVID-19 Drug Mol-nupiravir Electrochemical Determination over the Poly-((1,2,4-triazole)-co-(squaraine dye) Composite with Cobalt (III) Oxyhy-droxide. Biointerface Research in Applied Chemistry 13(1): 74-80. https://biointerfaceresearch.com/ google scholar
• Ueda, S., & Nagasawa, H. (2009). Facile Synthesis of 1,2,4-Triazoles via a Copper-Catalyzed Tandem Addition-Oxidative Cyclization. Journal of the American Chemical Society, 131(42):15080-15081. https://doi.org/10.1021/ja905056z google scholar
• Vagish, C.B., Sudeep, P., Jayadevappa, H.P. & Ajay Kumar, K. (2020). 1,2,4-Triazoles: synthetic and medicinal perspectives. In-ternational Journal of Current Research, 12(08): 12950-12960.https://doi.org/10.24941/ijcr.39386.08.2020 google scholar
• Valicsek, V.-S., & Badea, V. (2021). (R,S)-2-[4-(4-Methylphenyl)-5-phenyl-4H-1,2,4-triazol-3-yl]thio-1-phenyl-1-ethanol. Molbank, 2021, M1241. https://doi.org/10.3390/M1241 google scholar
• Wang, Y., He, M., Chen, B., & Hu, B. (2020). Hydroxyl-containing porous organic framework coated stir arsorption extraction com-bined with high performance liquid chromatography-diode ar-ray detector for analysis of triazole fungicides in grape and cabbage samples. Journal of Chromatography A 1633 461628 https://doi.org/10.1016/j.chroma.2020.461628 google scholar
• Wright, W.B.Jr., Press, J.B., Chan, P.S., Marsico, J.W., Haug, M.F., Lucas, J., Tauber, J., & Tomcufcik, A.S. (1986). Thrombox-ane synthetase inhibitors and antihypertensive agents. 1. N-[(1H-imidazol-1-yl)alkyl]aryl amides and N-[(1H-1,2,4-triazol-1-yl)alkyl]aryl amides. Journal of Medicinal Chemistry, 29(4):523-530. https://doi.org/10.1021/jm00154a017 google scholar
• Wu, J., Ni, T., Chai, X., Wang, T., Wang, H.... Jiang,Y. (2018). Molecular docking, design, synthesis and an-tifungal activity study of novel triazole derivatives. Eu-ropean Journal of Medicinal Chemistry 143: 1840-1846. https://doi.org/10.1016/j.ejmech.2017.10.081 google scholar
• Xie, F., Ni, T., Zhao, J., Pang, L., Li, R.... Jiang, Y. (2017). De-sign, synthesis, and in vitro evaluation of novel antifungal tria-zoles. Bioorganic & Medicinal Chemistry Letters, 27: 2171-2173. https://doi.org/10.1016/j.bmcl.2017.03.062 google scholar
• Y an, T., Jinchao, M., Yang, H., & Cheng, G. (2022). Introduction of energetic bis-1,2,4-triazoles bridges: A strategy towards ad-vanced heat resistant explosives. Chemical Engineering Journal, 429:132416. https://doi.org/10.1016/j.cej.2021.132416 google scholar
• Y ang, B., He, Q.J., & Zhu, D.Y. (2006). Antiproliferative activity of contragestazol (DL1112IT) in murine and human tumor models in vitro and in vivo. Cancer Chemotherapy and Pharmacology, 57: 268-273. https://doi.org/10.1007/s00280-005-0049-9 google scholar
• Y eung, K.S., & Farkas, M.E. (2005). A base-catalyzed, di-rect synthesis of 3,5-disubstituted 1,2,4-triazoles from ni-triles and hydrazides. Tetrahedron Letters, 46(19):3429-3432. https://doi.org/10.1016/j.tetlet.2005.02.167 google scholar
• Yin, P., Ma, W.B., Chen, Y., Huang, W.C., Deng, Y., & He, L. (2009). Highly efficient cyanoimidation of aldehydes. Organic Letters, 3(23):5482-5485. https://doi.org/10.1021/ol902207h google scholar
• Youichiro, N., Akahoshi, F., Takeda, S., Okada, T., Kajii, M., Nishimura, H., Sugiura, M., Fukaya, C., & Kagitani, Y. (1996). Synthesis and Pharmacological Activity of Triazole Deriva-tives Inhibiting Eosinophilia. Journal of Medicinal Chemistry, 39:3019-3029. https://doi.org/10.1021/jm9507993 google scholar
• Zazharskyi, V., Bigdan, O., Parchenko, V., Parchenko, M., Fotina, T., Davydenko, P.... Borovik, I. (2021). Antimicrobial Activity of google scholar
• Some Furans Containing 1,2,4-Triazoles. Archives of Pharmacy Practice, 12(2):60-5. https://doi.org/10.51847/RbJb3waUBB google scholar
• Zhang, H.Z., Damu, G.L.V., Cai, G.X., & Zhou, C.H. (2014). Current Developments in the Syntheses of 1,2,4-Triazole Compounds. Current Organic Chemistry, 18:359-406. https://doi.org/10.2174/13852728113179990025 google scholar
• Zhou, H.C. & Wang, Y. (2012). Recent researches in triazole compounds as medicinal drugs. Current Medicinal Chemistry, 19(2):239-280. https://doi.org/10.2174/092986712803414213 google scholar
• Zveaghintseva, M., Stingaci, E., Pogrebnoi, S., Smetanscaia, A., Valica, V., Uncu, L. ... Macaev, F.Z. (2021). Chromenol derivatives as novel antifungal agents: synthe-sis, in silico and in vitro evaluation. Molecules, 26(14):1-21. https://doi.org/10.3390/molecules26144304 google scholar