Mannich base of pyrazolines 3(a–e) under both conventional and microwave irradiation was synthesized. All the synthesised compounds were purified by recrystallisation, characterized on the basis of UV, IR, and NMR spectroscopy, and further supported by mass spectroscopy. The result obtained confirms superiority of microwave irradiation method over classical heating one. The molecular properties and Lipinski rule of five for compounds 3(a–e) were determined by Molinspiration. The synthesized compounds were subsequently evaluated for the antioxidant activity. All the compounds were found in compliance with Lipinski “Rule of Five”, and compound 3e having p-hydroxyl substitution showed best antioxidant activity as compared to ascorbic acid and rutin. 1. Introduction Variously substituted pyrazolines and their derivatives are important biological agents, and a significant amount of research activity has been directed towards this class. In particular, they are used as antibacterial [1], antifungal [2], anti-inflammatory [3], central nervous system depressant [4], analgesic [5], mono amino oxidase inhibitor [6], anticancer [7], and antiviral agents [8]. Moreover, pyrazolines have played a crucial part in the development of theory in heterocyclic chemistry. The advantages of microwave technology over conventional method have promoted us to synthesize pyrazolines from both conventional as well as microwave assisted method. There are several medical emergencies that result from free radical mediated pathology. The purpose of this study was to synthesize the pyrazoline derivatives in search for exploring the potential of this skeleton as antioxidant. 2. Materials and Methods All the melting points reported were determined in open capillaries using Veego VMP-1 melting point apparatus expressed in °C and are uncorrected. The I. R. spectra of the compounds were recorded on Perkin-Elmer infrared 283 spectrometer in KBr disc and expressed in cm？1. NMR spectra were recorded on Bruker DRX-300 spectrometer. Mass spectra were recorded on Jeol SX-102 (FAB) spectrometer. Synthesis and analytical studies of title compounds were carried out using laboratory grade reagents. Standard techniques like TLC were used to monitor reactions and to determine purity of the products. All the products were purified by recrystallization. The microwave-assisted syntheses were carried out in domestic oven, Midea PJ21B-A 400？W. All the compounds were subjected to molecular properties prediction and drug-likeness by Molinspiration software. 2.1. Procedure for Synthesis 2.1.1. Step？？1:
References
[1]
E. M. Sharshira and N. M. M. Hamada, “Synthesis and antimicrobial evaluation of some pyrazole derivatives,” Molecules, vol. 17, no. 5, pp. 4962–4971, 2012.
[2]
H. Deng, Z. Y. Yu, G. Y. Shi, M. J. Chen, K. Tao, and T. Hou, “Synthesis and in vitro antifungal evaluation of 1,3,5-trisubstituted-2-pyrazoline derivatives,” Chemical Biology and Drug Design, vol. 79, no. 3, pp. 279–289, 2012.
[3]
M. Amir, H. Kumar, and S. A. Khan, “Synthesis and pharmacological evaluation of pyrazoline derivatives as new anti-inflammatory and analgesic agents,” Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 3, pp. 918–922, 2008.
[4]
Z. Ozdemir, H. B. Kandilci, B. Gumusel, U. Calis, and A. A. Bilgin, “Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-thienyl)pyrazoline derivatives,” Archiv der Pharmazie, vol. 341, no. 11, pp. 701–707, 2008.
[5]
S. Sridhar and Y. Rajendraprasad, “Synthesis and analgesic studies of some new 2-pyrazolines,” E-Journal of Chemistry, vol. 9, no. 4, pp. 1810–1815, 2012.
[6]
M. Karuppasamy, M. Mahapatra, S. Yabanoglu et al., “Development of selective and reversible pyrazoline based MAO-A inhibitors: synthesis, biological evaluation and docking studies,” Bioorganic and Medicinal Chemistry, vol. 18, no. 5, pp. 1875–1881, 2010.
[7]
R. Bashir, S. Ovais, S. Yaseen et al., “Synthesis of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide as anticancer and anti-inflammatory agents,” Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 14, pp. 4301–4305, 2011.
[8]
A. E. E. Amr, N. A. Abdel-Latif, and M. M. Abdalla, “Synthesis and antiandrogenic activity of some new 3-substituted androstano[17,16-c]-5′-aryl-pyrazoline and their derivatives,” Bioorganic and Medicinal Chemistry, vol. 14, no. 2, pp. 373–384, 2006.
[9]
S. Syam, S. I. Abdelwahab, M. A. Al-Mamary, and S. Mohan, “Synthesis of chalcones with anticancer activities,” Molecules, vol. 17, no. 6, pp. 6179–6195, 2012.
[10]
Molinspiration Cheminformatics [Homepage on the Internet], Nova Ulica, Slovensky Grob, Slovakia, 2012, http://www.molinspiration.com/.
[11]
P. Ertl, B. Rohde, and P. Selzer, “Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties,” Journal of Medicinal Chemistry, vol. 43, no. 20, pp. 3714–3717, 2000.
[12]
D. F. Veber, S. R. Johnson, H. Cheng, B. R. Smith, K. W. Ward, and K. D. Kopple, “Molecular properties that influence the oral bioavailability of drug candidates,” Journal of Medicinal Chemistry, vol. 45, no. 12, pp. 2615–2623, 2002.
[13]
S. Sreejayan and M. N. A. Rao, “Oxygen free radical scavenging activity of the juice of Momordica charantia fruits,” Fitoterapia, vol. 62, no. 4, pp. 344–346, 1991.
[14]
L. Marcocci, J. J. Maguire, M. T. Droy-Lefaix, and L. Packer, “The nitric oxide-scavenging properties of Ginkgo biloba extract EGb 761,” Biochemical and Biophysical Research Communications, vol. 201, no. 2, pp. 748–755, 1994.
[15]
C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings,” Advanced Drug Delivery Reviews, vol. 23, no. 1–3, pp. 3–25, 1997.
