Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles

Kishor Palleapati; Venkata Kancharlapalli; Afzal Shaik

Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. TB is a global problem and is one of the major culprits responsible for the death of many in the developing world despite the availability of more than 20 drugs. Hence, there is an imperative need for the development of novel antitubercular drugs. To develop better agents against tuberculosis, we synthesized a series of dihydropyrazole-1-carboxamides by the base-catalyzed condensation of isoxazolyl chalcones with semicarbazide. The compounds were purified by column chromatography and characterized by spectral methods including IR, 1H NMR, 13C NMR and elemental analysis. The antitubercular activity was screened against Mycobacterium tuberculosis by MABA assay where isoniazid was used as positive control for comparing the activity. The studies revealed that isoxazole-1-carboxamides were more active compared to the corresponding chalcones. Substituents on the phenyl ring at position-5 of isoxazole ring played a crucial role in determining the antitubercular potency. The compounds 4n and 4o containing a blend of halogen and methoxyl groups at ortho and para positions of phenyl ring showed potency greater than the standard, isoniazid with MIC of 0.1 µg/mL and emerged as promising leads against TB. Further, 4n and 4o were assessed for their cytotoxic effects on L02 (human normal cell line) by using MTT assay. The compounds showed no cytotoxicity and established the safety of these compounds.

Keywords

References

[1] WHO Global tuberculosis report 2017. http://www.who.int/mediacentre/news/releases/2017/politicalcommitment-tb/en/ (accessed on November 02, 2017).
[2] Varghese B, Al-Busafi SN, Suliman FO, Al-Kindy SMZ. Unveiling a versatile heterocycle: pyrazoline–a review. RSC Adv. 2017; 7(74): 46999-47016. [CrossRef]
[3] Bhutani R, Pathak DP, Husain A, Kapoor G, Kant R. A review on recent development of pyrazoline as a pharmacologically active molecule. Int J Pharm Sci Res. 2015; 6(10): 4113-4128. [CrossRef]
[4] Sharma S, Sandeep K, Tania B, Jyoti G. Review on synthesis of bioactive pyrazoline derivatives. Chem Sci Trans. 2014; 3(3): 861-875. [CrossRef]
[5] Akranth M, Mohammed RA, Mohammed TA, Rikta S, Omprakash T, Mymoona A, Mohammed S, Mumtaz MA. Pyrazolines: A Biological Review. Mini Rev Med Chem. 2013; 6(13): 921-931. [CrossRef]
[6] Suresh K, Sandhya B, Sushma D, Rajiv K, Himanshu G. Biological activities of pyrazoline derivatives-A recent development. Recent Pat Antiinfect Drug Discov. 2009; 4(3): 154-163. [CrossRef]
[7] 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. [CrossRef]
[8] Viveka S, Dinesha, Shama P, Nagaraja GK, Ballav S, Kerkar S. Design and synthesis of some new pyrazolylpyrazolines as potential anti-inflammatory, analgesic and antibacterial agents. Eur J Med Chem. 2015; 101: 442-451. [CrossRef]

[9] Rostom SA, Badr MH, Abd El Razik HA, Ashour HM, Abdel Wahab AE. Synthesis of some pyrazolines and pyrimidines derived from polymethoxy chalcones as anticancer and antimicrobial agents. Arch Pharm (Weinheim). 2011; 344(9): 572-587. [CrossRef]
[10] Küçükoğlu K, Oral F, Aydın T, Yamalı C, Algül Ö, Sakagami H, Gülçin İ, Supuran CT, Gül Hİ. Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines. J Enzym Inhib Med Chem. 2016; 31(sup4): 20-24. [CrossRef]
[11] George RF, Fouad MA, Gomaa IEO. Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers. Eur J Med Chem. 2016; 112: 48-59. [CrossRef]
[12] Montoya A, Quiroga J, Abonia R, Nogueras M, Cobo J, Insuasty B. Synthesis and in vitro antitumor activity of a novel series of 2-pyrazoline derivatives bearing the 4-aryloxy-7-chloroquinoline fragment. Molecules. 2014; 19(11): 18656-18675. [CrossRef]
[13] Muneera MS, Joseph J. Design, synthesis, structural elucidation, pharmacological evaluation of metal complexes with pyrazoline derivatives. J Photoch Photobio B. 2016; 163: 57-68. [CrossRef]
[14] Abid M, Azam A. 1-N-substituted thiocarbamoyl-3-phenyl-2-pyrazolines: synthesis and in vitro antiamoebic activities. Eur J Med Chem. 2005; 40(9): 935-942. [CrossRef]
[15] Bandgar BP, Adsul LK, Chavan HV, Jalde SS, Shringare SN, Shaikh R, Meshram RJ, Gacche RN, Masand V. Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett. 2012; 22(18): 5839-5844. [CrossRef]
[16] Bhosle MR, Deshmukh AR, Pal S, Srivastava AK, Mane RA. Synthesis of new thiazolylmethoxyphenyl pyrimidines and antihyperglycemic evaluation of the pyrimidines, analogues isoxazolines and pyrazolines. Bioorg Med Chem Lett. 2015; 25(11): 2442-2446. [CrossRef]
[17] Acharya BN, Saraswat D, Tiwari M, Shrivastava AK, Ghorpade R, Bapna S, Kaushik MP. Synthesis and antimalarial evaluation of 1,3,5-trisubstituted pyrazolines. Eur J Med Chem. 2010; 45(2): 430-438. [CrossRef]
[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. [CrossRef]
[19] Dixit SR, Joshi SD, Kulkarni VH. Pyrrolyl pyrazoline carbaldehydes as enoyl-ACP reductase inhibitors: Design, synthesis and antitubercular activity. The Open Med Chem J. 2017; 11: 92-108. [CrossRef]
[20] Sharad KC, Vishal BP, Parth T, Vasudev T, Raval DK. Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities. Eur J Med Chem. 2016; 112: 270-279. [CrossRef]
[21] Ahsan MJ, Saini V. Design and synthesis of 3-(4-aminophenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide/carbothioamide analogues as antitubercular agents. Beni-Suef J Bas App Sci. 2015; 4(1): 41-46. [CrossRef]
[22] Aftab A, Asif H, Shah AK, Mohammed M, Anil B. Synthesis, antimicrobial and antitubercular activities of some novel pyrazoline derivatives. J Saudi Chem Soc. 2016; 20(5): 577-584. [CrossRef]
[23] Gupta RA, Kashedikar SG. Synthesis, antitubercular activity, and QSAR analysis of substituted nitroaryl analogs: Chalcone, pyrazole, isoxazole, and pyrimidines. Med Chem Res. 2013; 22(8): 3863-3880. [CrossRef]
[24] Ahsan MJ, Samy JG, Khalilullah H, Bakht MA, Hassan MZ. Synthesis and antimycobacterial evaluation of 3a,4-dihydro-3H-indeno[1,2-c]pyrazole-2-carboxamide analogues. Eur J Med Chem. 2011; 46(11): 5694-5697. [CrossRef]
[25] Pallepati K, Venkata RK, Afzal BS. Antitubercular evaluation of isoxazolyl chalcones. Res J Pharm Biol Chem Sci. 2017; 8(6): 730-735.
[26] Rajendra Prasad Y, Lakshmana Rao A, Prasoona L, Murali K, Ravi Kumar P. Synthesis and antidepressant activity of some 1,3,5-triphenyl-2-pyrazolines and 3-(2″-hydroxynaphthalen-1″-yl)-1,5-diphenyl-2-pyrazolines. Bioorg Med Chem Lett. 2005; 15(22): 5030-5034. [CrossRef]
[27] Khode S, Maddi V, Aragade P, Palkar M, Ronad PK, Mamledesai S, Thippeswamy AH, Satyanarayana D. Synthesis and pharmacological evaluation of a novel series of 5-(substituted)aryl-3-(3-coumarinyl)-1-phenyl-2-pyrazolines as novel anti-inflammatory and analgesic agents. Eur J Med Chem. 2009; 44(4): 1682-1688. [CrossRef]
[28] Hearn MJ. PCT Int. Appl. 2002, WO 02043668; Chem. Abstr. 2002; 137:20296.
[29] Goto S, Jo K, Kawakita T, Misuhashi S, Nishino T, Ohasawa N, Tanami N. Determination method of minimum inhibitory concentrations. Chemotherapy 1981; 29: 76–79.

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Kishor Palleapati ^* This is me
India

Venkata Kancharlapalli This is me
India

Afzal Shaik
India

Publication Date

June 27, 2025

Submission Date

April 6, 2018

Acceptance Date

September 12, 2018

Published in Issue

Year 2019 Volume: 23 Number: 2

IZ

https://izlik.org/JA83DN74LT

Cite

RIS / Bibtex

APA

Palleapati, K., Kancharlapalli, V., & Shaik, A. (2025). Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles. Journal of Research in Pharmacy, 23(2), 156-163. https://izlik.org/JA83DN74LT

AMA

1.Palleapati K, Kancharlapalli V, Shaik A. Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles. J. Res. Pharm. 2025;23(2):156-163. https://izlik.org/JA83DN74LT

Chicago

Palleapati, Kishor, Venkata Kancharlapalli, and Afzal Shaik. 2025. “Synthesis, Characterization and Antitubercular Evaluation of Some New Isoxazole Appended 1-Carboxamido-4,5-Dihydro-1H-Pyrazoles”. Journal of Research in Pharmacy 23 (2): 156-63. https://izlik.org/JA83DN74LT.

EndNote

Palleapati K, Kancharlapalli V, Shaik A (June 1, 2025) Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles. Journal of Research in Pharmacy 23 2 156–163.

IEEE

[1]K. Palleapati, V. Kancharlapalli, and A. Shaik, “Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles”, J. Res. Pharm., vol. 23, no. 2, pp. 156–163, June 2025, [Online]. Available: https://izlik.org/JA83DN74LT

ISNAD

Palleapati, Kishor - Kancharlapalli, Venkata - Shaik, Afzal. “Synthesis, Characterization and Antitubercular Evaluation of Some New Isoxazole Appended 1-Carboxamido-4,5-Dihydro-1H-Pyrazoles”. Journal of Research in Pharmacy 23/2 (June 1, 2025): 156-163. https://izlik.org/JA83DN74LT.

JAMA

1.Palleapati K, Kancharlapalli V, Shaik A. Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles. J. Res. Pharm. 2025;23:156–163.

MLA

Palleapati, Kishor, et al. “Synthesis, Characterization and Antitubercular Evaluation of Some New Isoxazole Appended 1-Carboxamido-4,5-Dihydro-1H-Pyrazoles”. Journal of Research in Pharmacy, vol. 23, no. 2, June 2025, pp. 156-63, https://izlik.org/JA83DN74LT.

Vancouver

1.Kishor Palleapati, Venkata Kancharlapalli, Afzal Shaik. Synthesis, characterization and antitubercular evaluation of some new isoxazole appended 1-carboxamido-4,5-dihydro-1H-pyrazoles. J. Res. Pharm. [Internet]. 2025 Jun. 1;23(2):156-63. Available from: https://izlik.org/JA83DN74LT