Volume : 09, Issue : 07, July – 2022
Title:
02.DESIGN, SYNTHESIS, CHARACTERIZATION AND ANTIBACTERIAL EVALUATION OF TRISUBSTITUTED 4,5-DIHYDROPYRAZOLES DERIVATIVES
Authors :
Ashok Vishwakarma, Alok Pal Jain, Sandeep Patel
Abstract :
Objective: The objective of the paper is to design, synthesis and characterization of trisubstituted 4,5-dihydropyrazoles and evaluated for their antibacterial activity.
Material and methods: The derivatives have been synthesized by the two steps process, in first step 1-(4-aminophenyl)ethan-1-one (0.002M) (1) react with 4-substituted benzaldehyde (2) to form (E)-1-(4-substituted phenyl)-3-(p-substituted)prop-2-en-1-one [3]. The final compound (4), 1-(4-substitutedphenyl)-3-(4-substitutedphenyl)-5-(p-substituted)-4,5-dihydro-1H-pyrazole was synthesized by the reaction of compound 3 with different (4-fluorophenyl) hydrazine and (4-chlorophenyl) hydrazine. Total Sixteen compounds have been synthesized and characterized by physicochemical and spectral analysis. The final compounds (TDHP-1 to TDHP-16) have been evaluated for antibacterial activity by disk diffusion method.
Result and Discussion: The synthesized compounds have characterized by the IR, 1HNMR and mass spectral analysis. The IR spectrum of the compounds has shown the characteristics peak (cm-1) at 3012 (C–H), 2912 (C–H), 1675 (C=C), 1595 (C-C), 1462 (C=N), 1308 (C-H), 1512 (N=O), 1334 (N-O), 745 (C-Cl), 1018 (C-Br); 1102 (C-F). The 1HNMR spectra of synthesized compounds depicted the peak at δ7.23-8.62 (m, 4H, CH=CH-CH=CH), 7.03-8.80 (m, 3H, Ar-H), 3.08, 2.47 (d, 2H, CH2), 3.42 (d, 1H, C-5, CH), 11.431 (s, 1H, NH). The Data of antibacterial activity against the gram-positive bacterial strains (Bacillus subtilis and Staphylococcus aureus) suggested that among substituted pyrazoline derivatives (TDHP-1 to TDHP-16), compound TDHP-2, TDHP-3, TDHP-4, TDHP-5, TDHP-6, TDHP-7, TDHP-8 have shown best activity against gram positive bacteria and The Data of antibacterial activity against the gram-negative bacterial strains (Salmonella typhimurium and Pseudomonas aeruginosa) suggested that among substituted pyrazoline derivatives (TDHP-1 to TDHP-16), compound TDHP-1, TDHP-2, TDHP-3, TDHP-4, TDHP-5 TDHP-6, TDHP-7, TDHP-8 have shown best activity against gram negative bacteria.
Conclusion: In general, trisubstituted 4,5-dihydropyrazoles derivatives having amine termination has shown the better anti-microbial activity as compared to standard drug. There is a need in drug design strategy to achieve more anti-microbial potency in different bacterial strain on novel future synthetic heterocyclic compounds.
Keywords: Antimicrobial activity, disk diffusion method, antibacterial, pyrazole, gram positive
Cite This Article:
Please cite this article in press Ashok Vishwakarma et al, Design, Synthesis, Characterization And Antibacterial Evaluation Of Trisubstituted 4,5-Dihydropyrazoles Derivatives., Indo Am. J. P. Sci, 2022; 09(7).,
Number of Downloads : 10
References:
1. 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.
2. 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
3. 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.
4. 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.
5. 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.
6. Jain SK, Singhal R, Jain NK. Synthesis, characterization and biological activity of pyrazoline derivatives. Res J Pharm Tech 2021; 14(12):6223-7.
7. 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.
8. 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.
9. 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.
10. 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.
11. Kumari R, Kumar A. Synthesis and In-Vitro Anti-Inflammatory Activity of New Pyrazoline Derivatives. Research J Pharm Tech 2018; 11(9): 3969-3972
12. 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.
13. Ansari A, Ali A, Mohammad A. Biologically active pyrazole derivatives. New J Chem 2017; 41(1): 16-41.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. Dar KN, Ayaz M, Siddiqui N, & Rehman, Sumbul. Synthesis, characterization, antimicrobial and anticancer studies of new steroidal pyrazolines. Journal of Saudi Chemical Society 2016; 20(1): 7-12.
21. Hamada NMM, Abdo NYM. Synthesis, characterization, antimicrobial screening and free-radical scavenging activity of some novel substituted pyrazoles. Molecules 2015; 20(6): 10468–10486.
22. Samshuddin S, Narayana B, Sarojini BK, Khan MTH, Yathirajan HS, Raj CGD, Raghavendra R. Antimicrobial, analgesic, DPPH scavenging activities and molecular docking study of some 1,3,5-triaryl-2-pyrazolines. Med Chem Res 2012; 21(8): 2012–2022.
23. Manna K, Agrawal YK. Microwave assisted synthesis of new indophenazine 1,3,5 tri substituted pyrazoline derivatives of benzofuran and their antimicrobial activity. Bioorg Med Chem Lett 2009; 19(10): 2688–2692.