Synthesis and Characterization of trisubstituted 4,5-dihydropyrazoles and evaluated for their antimicrobial activity
Keywords:
Pharmaceutical Chemistry, Drug Discovery, Α,Β-Unsaturated Ketone, Chalcones, Trisubstituted 4, 5-Dihydropyrazoles, Antimicrobial Activity, Heterocyclic Compounds, Synthetic Chemistry, Antibacterial Agents, Anti-Inflammatory, Anticancer
Abstract
Pharmaceutical chemistry is predominantly focused on drug discovery and development. Among the vast array of bioactive compounds, α,β-unsaturated ketones, particularly chalcones, represent an essential class of naturally occurring flavonoids with diverse pharmacological properties. In this study, different 4-substituted benzaldehydes, specifically (4-fluorophenyl) hydrazine and (4-chlorophenyl) hydrazine, were utilized to synthesize a series of novel trisubstituted 4,5-dihydropyrazole derivatives. The synthesized compounds were structurally characterized using standard spectroscopic techniques, confirming the successful formation of the targeted heterocyclic frameworks. The antimicrobial activity of these new derivatives was evaluated against various bacterial strains. Results indicated that the compounds exhibited a spectrum of antimicrobial efficacy ranging from mild to significant, with the trisubstituted 4,5-dihydropyrazole derivatives bearing amine terminations displaying superior antimicrobial activity when compared to standard drugs. This suggests their potential as potent antimicrobial agents. The findings emphasize the need for continued optimization in drug design strategies to enhance antimicrobial potency across a broader range of bacterial strains. Additionally, future work should involve testing these novel compounds in diverse biological assays to explore their therapeutic potential in other areas, such as anti-inflammatory and anticancer activities, particularly against carcinoma cell lines. This study underscores the importance of synthetic heterocyclic compounds in the development of novel therapeutics.
References
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32. Khazaal & Tomma. Synthesis and Characterization of Novel Schiff Bases Containing Isoxazoline or Pyrazoline Unit. Ibn AL-Haitham Journal for Pure and Applied Science2017; 24(2): 338-345.
33. Fioravanti R, Desideri N, Carta A, Atzori EM, Delogu I, Collu G, Loddo R. Inhibitors of Yellow Fever Virus replication based on 1,3,5-triphenyl-4,5-dihydropyrazole scaffold: design, synthesis and antiviral evaluation. Eur J Med Chem 2017;141: 15–25.
34. Gul HI, Mete E, Taslimi P, Gulcin I, Supuran CT. Synthesis, carbonic anhydrase I and II inhibition studies of the 1,3,5-trisubstituted-pyrazolines. J Enzyme Inhib Med Chem 2017; 32(1): 189–192.
35. Mishra VK, Mishra M, Kashaw V, Kashaw SK. Synthesis of 1, 3, 5 trisubstituted pyrazolines as potential antimalarial and antimicrobial agents. Bioorg. Med. Chem. 2017; 25(6): 1949–1962.
36. Sadashiva R, Naral D, Kudva J, Shivalingegowda N, Lokanath NK, Pampa KJ. Synthesis, spectral, biological activity, and crystal structure evaluation of novel pyrazoline derivatives having sulfonamide moiety. Med Chem Res 2017; 26(6): 1213–1227.
2. Jimi MA, Raj K. 4,5-Dihydro-1H-pyrazole: An indispensable scaffold. J Enzyme Inhib Med Chem 2014; 29: 427-442.
3. RamirezPrada J, Robledo SM, Velez ID, Crespo MDP, Quiroga J, Abonia R, Montoya A, Svetaz L, Zacchino S, Insuasty B. Synthesis of novel quinoline-based 4,5-dihydro-1-H-pyrazoles as potential anticancer, antifungal, antibacterial, antiprotozoal agents. Med Chem 2017; 131: 237-254.
4. Sowmya DV, Lakshmi Teja A, Padmaja A, Kamala Prasad V, Padmavathi V. Green approach for the synthesis of thiophenyl pyrazoles and isoxazoles by adopting 1,3 dipolar cycloaddition methodology and their antimicrobial activity. Eur J Med Chem 2018; 143: 891–898
5. Pallepati K, Venkata RK, Afzal BS. Antitubercular evaluation of isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles. J Res Pharm 2019; 23: 156-163.
6. Lavanya G, Mallikarjunareddy L, Padmavathi V, Padmaja A. Synthesis and antimicrobial activity of (1,4-phenylene)bis(arylsulfonylpyrazoles and isoxazoles). Eur J Med Chem 2014; 73: 187–194.
7. Abdelhamid AO, EI Sayed IE, Zaki YH, Hussein AM, Mangoud MM, Hosny MA. Utility of 5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide in the synthesis of heterocyclic compounds with antimicrobial activity. Biorg Med Chem 2019; 13: 48.
8. Hassan SY. Synthesis, antibacterial and antifungal activity of some new pyrazoline and pyrazole derivatives. Molecules 2013; 18: 2683–2711.
9. Hai-Chao W, Xiao-Qiang Y, Tian-Long Y, Hong-Xia L, Zhong-Chang W, Hai-Liang Z. Design, Synthesis and Biological Evaluation of Benzohydrazide Derivatives Containing Dihydropyrazoles as Potential EGFR Kinase Inhibitors. Molecules 2016; 21: 1012
10. Vanessa G, Sidnei M, Alex FCF, Darlene CF, Pio C, Ernani P. Antioxidant and Antimicrobial Properties of 2-(4,5-Dihydro-1H-pyrazol-1-yl)-pyrimidine and 1-Carboxamidino-1H-pyrazole Derivatives. J Braz Chem Soc 2010; 21: 1477–1483.
11. Shah Z, MohammedZ, Hingole A. An introduction of some novel pyrazolinesto synthetic chemistry and antimicrobial studies. JChem Pharma Res2010; 2(6): 441-445.
12. GencY, Ozkanca R, Bekdemir Y. Antimicrobial activity ofsome sulfonamide derivatives on clinical isolates of Staphylococusaureus. Ann. Clin. Microbiol. Antimicrob. 2008; 7(1): 1–6
13. Gul HI, Yamali C, Yesilyurt F, Sakagami H, KucukogluK,Gulcin I, Gul M, Supuran CT. Microwave-assistedsynthesis and bio-evaluation of new sulfonamides. J Enzyme InhibMed Chem 2017; 32(1): 369–374.
14. Hamada NMM, Abdo NYM. Synthesis, characterization,antimicrobial screening and free-radical scavenging activity of somenovel substituted pyrazoles. Molecules 2015; 20(6):10468–10486.
15. Khanam S, Dar H, Siddiqui AM, Rehman N. Synthesis, characterization, antimicrobial and anticancerstudies of new steroidal pyrazolines. J Saudi Chem Soc 2015; 20(1): 7-12.
16. Mishra VK, Mishra M, Kashaw V, Kashaw SK.Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents. Bioorg. Med. Chem. 2017; 25(6): 1949–1962.
17. Samshuddin S, Narayana B, Sarojini BK, Khan MTH, Yathirajan HS, Raj CGD,Raghavendra R. Antimicrobial,analgesic, DPPH scavenging activities and molecular docking studyof some 1,3,5-triaryl-2-pyrazolines. Med Chem Res 2012; 21 (8), 2012-2022.
18. Thach TD, Le T, Nguyen TA, Dang CH, Dang VS,Nguyen TD. Synthesis of sulfonamides bearing 1,3,5-triarylpyrazoline and 4-thiazolidinone moieties as novel antimicrobial agents. J Serb ChemSoc 2020; 85(2), 155–162.
19. Akhtar W, Marella A, Alam MM, Khan MF, Akhtar M, Anwer T, Khan F, Naematullah M, Azam F, Rizvi MA, Shaquiquzzaman M. Design and synthesis of pyrazole pyrazoline hybrids as cancer-associated selective COX-2 inhibitors. Arch Pharm 2021; 354 (1): 2000116.
20. Jain SK, Singhal R, Jain NK. Synthesis, characterization and biological activity of pyrazoline derivatives. Res J Pharm Tech 2021; 14(12):6223-7.
21. Moqbel RMA, Gitima D, Meriyam V M. Synthesis and molecular docking studies of some new pyrazoline derivatives for antimicrobial properties. Res J Pharm Tech 2020; 13(10): 4629-34.
22. Thach TD, Le T, Nguyen TA, Dang CH, Dang VS, Nguyen TD. Synthesis of sulfonamides bearing 1,3,5- triarylpyrazoline and 4-thiazolidinone moieties as novel antimicrobial agents. J Serb Chem Soc 2020; 85(2): 155–162.
23. Prabha T, Aishwaryah P, Manickavalli E, Chandru R, Arulbharathi G, Anu A, Sivakumar T. A Chalcone Annulated Pyrazoline Conjugates as a Potent Antimycobacterial Agents: Synthesis and in Silico Molecular Modeling Studies. Research J Pharm Tech 2019; 12(8): 3857-65.
24. Ozmen Ozgun D, Gul HI, Yamali C, Sakagami H, Gulcin I, Sukuroglu M, Supuran CT. Synthesis and bioactivities of pyrazoline benzene-sulfonamide as carbonic anhydrase and acetylcholinesterase inhibitors with low cytotoxicity. Bioorg. Chem. 2019; 84: 511–517.
25. Kumar P, Kumar A, Nayak P, Pinto JS, D’Souza B. Synthesis and Antimicrobial Evaluation of some Novel Pyrazoline Incorporated Pyrrole Derivatives. Research J Pharm Tech 2018; 11(6): 2460-2462.
26. Kumari R, Kumar A. Synthesis and In-Vitro Anti-Inflammatory Activity of New Pyrazoline Derivatives. Research J Pharm Tech 2018; 11(9): 3969-3972
27. Naim MJ, Alam O, Alam MJ, Hassan MQ, Siddiqui N, Naidu VGM, Alam MI. Design, synthesis and molecular docking of thiazolidinedione based benzene sulphonamide derivatives containing pyrazole core as potential anti-diabetic agents. Bioorg Chem 2018; 76: 98–112.
28. Ansari A, Ali A, Mohammad A. Biologically active pyrazole derivatives. NewJ Chem2017; 41(1): 16-41.
29. Bhat KI, Kumar A. Synthesis and Biological Evaluation of Some Novel Pyrazoline Derivatives Derived from Chalcones. Research J Pharm Tech 2017; 10(5): 1344-1346.
30. Revanasiddappa BC, Vijay Kumar M, Nayak P, Ali AR, Jisha MS. Synthesis, Antibacterial and Antifungal Evaluation of Novel Pyrazoline Derivatives. Research J Pharm Tech 2017; 10(5): 1481-1484.
31. Fernandes J, Revanasiddappa BC, Bhat KI, Vijay Kumar M, D’Souza L, Alva SS. Synthesis and in-Vitro Anti-Inflammatory Activity of Novel Pyrazoline Derivatives. Research J Pharm Tech 2017; 10(6):1679-1682.
32. Khazaal & Tomma. Synthesis and Characterization of Novel Schiff Bases Containing Isoxazoline or Pyrazoline Unit. Ibn AL-Haitham Journal for Pure and Applied Science2017; 24(2): 338-345.
33. Fioravanti R, Desideri N, Carta A, Atzori EM, Delogu I, Collu G, Loddo R. Inhibitors of Yellow Fever Virus replication based on 1,3,5-triphenyl-4,5-dihydropyrazole scaffold: design, synthesis and antiviral evaluation. Eur J Med Chem 2017;141: 15–25.
34. Gul HI, Mete E, Taslimi P, Gulcin I, Supuran CT. Synthesis, carbonic anhydrase I and II inhibition studies of the 1,3,5-trisubstituted-pyrazolines. J Enzyme Inhib Med Chem 2017; 32(1): 189–192.
35. Mishra VK, Mishra M, Kashaw V, Kashaw SK. Synthesis of 1, 3, 5 trisubstituted pyrazolines as potential antimalarial and antimicrobial agents. Bioorg. Med. Chem. 2017; 25(6): 1949–1962.
36. Sadashiva R, Naral D, Kudva J, Shivalingegowda N, Lokanath NK, Pampa KJ. Synthesis, spectral, biological activity, and crystal structure evaluation of novel pyrazoline derivatives having sulfonamide moiety. Med Chem Res 2017; 26(6): 1213–1227.
Published
2024-08-22
How to Cite
KM. Dipika, Dr. Arun Patel, Dr. Shailendra Patel, & Dr. Aditya Sahu. (2024). Synthesis and Characterization of trisubstituted 4,5-dihydropyrazoles and evaluated for their antimicrobial activity. Revista Electronica De Veterinaria, 25(1S), 461-478. Retrieved from https://veterinaria.org/index.php/REDVET/article/view/707
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