SYNTHESIS, IN SILICO PHYSICOCHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITIES OF SOME PYRAZOLINE DERIVATIVES
Objectives: Nitrogen containing heterocyclic compounds plays an important role in medicinal chemistry. Among them, five-membered ring pyrazolines have found to possess many biological and pharmacological activities like anticancer, antitubercular, antimicrobial, anti-inflammatory etc. Objective is to determine the physicochemical and drug like properties of the synthesized pyrazolines by in silico methods and to screen their antidiabetic and antioxidant activities.
Methods: Chalcones were synthesized from naphthaldehydes by condensing with various substituted acetophenones in ethanol and cyclized into pyrazolines using semicarbazides/thiosemicarbazides by conventional and microwave oven synthesis. The physicochemical and drug like properties were determined by using computational tools. Antidiabetic activity was evaluated by alpha amylase inhibition assay method. Antioxidant activity studies were done by DPPH and nitric oxide method.
Results: Pyrazolines were synthesized from chalcones. Microwave irradiated synthesis of chalcone was carried out to get higher yield with less reaction time period as compared to conventional method. The synthesized pyrazolines produces yield around 68% (conventional) and 85% (microwave). In silico studies showed considerable values satisfying all the parameters of physicochemical and Lipinskiâ€™s rule of five properties.Â Among the compounds tested for antidiabetic and antioxidant studies, some showed promising activity.
Conclusion: Physiochemical and drug like properties revealed that these compounds have good bioavailability and druglikeness properties. So these compounds are found to be interesting lead molecules for further synthesis as antidiabetic and antioxidant agents.
Keywords: Chalcones, pyrazolines, in silico physicochemical properties, biological activities.
Table 4: Antioxidant activity of pyrazolines
Inhibition level, % at 200 Î¼M
DPPH: 2,2â€‘diphenylâ€‘1â€‘picrylhydrazyl, NO: Nitric oxide2014;7(4):237-9.
2. Reddy LS, Raju MB, Sridhar C. Novel pyrazolines: Synthesis and evaluation of their derivatives with anticancer and anti-inflammatory activities. Int J Pharm Pharm Sci 2016;8(1):247-54.
3. Jacob KS, Ganguly S. A battle against aids: New pyrazole key to an older lock-reverse transcriptase. Int J Pharm Pharm Sci 2016;8(11):75-9.
4. Taj T, Kamble RR, Gireesh TM, Hunnur RK, Margankop SB. One-pot synthesis of pyrazoline derivatised carbazoles as antitubercular, anticancer agents, their DNA cleavage and antioxidant activities. Eur J Med Chem 2011;46(9):4366-73.
5. Kumar A, Bhat G, Varadaraj BG, Rajeev K, Singla RK. Synthesis and evaluation of antioxidant activity of novel 3, 5-disubstituted-2-pyrazolines. Bull Fac Pharm Cairo Univ 2013;51(2):167-73.
6. Babu VH, Sridevi CH, Joseph A, Srinivasan KK. Synthesis and biological evaluation of some novel pyrazolines. Indian J Pharm Sci 2007;69(3):470-3.
7. Lone IH, Khan KZ, Fozdar BI. Synthesis, physicochemical properties, antimicrobial and antioxidant studies of pyrazoline derivatives bearing a pyridyl moiety. Med Chem Res. DOI: 10.1007/s00044-013-0643-z.
8. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002;45(12):2615-23.
9. Lipinski CA. Lead-and drug-like compounds: The rule-of-five revolution. Drug Discov Today Technol 2004;1(4):337-41.
10. Muegge I. Selection criteria for drug-like compounds. Med Res Rev 2003;23(10):302-21.
11. Eichler HG, Korn A, Gasic S, Pirson W, Businger J. The effect of a new specific alpha-amylase inhibitor on post-prandial glucose and insulin excursions in normal subjects and Type 2 (Non-insulin-dependent) diabetic patients. Diabetologia 1984;26(4):278-81.
12. Chanda S, Dave R. In vitro models for antioxidant activity evaluation and some medicinal plants possessing antioxidant properties: An overview. Afr J Microbiol Res 2009;3(13):981.
13. Jainey PJ, Bhat KI. Microwave assisted synthesis of novel pyrimidines bearing benzene sulfonamides and evaluation of anticancer and antioxidant activities. Asian J Pharm Clin Res 2014;7(4):111-4.
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