Synthesis and SAR Studies of Bisthiourea Derivatives of Dipeptides Lys/lys-Asp, Lys/lys-Trp Conjugated Benzo[d]isoxazole as Promising Antioxidants
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A novel series of bisthiourea derivatives of four dipeptides consisting of Lys-Asp, lys-Asp, Lys-Trp and lys-Trp conjugated to 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole were synthesized and characterized by physical method and spectroscopic data. The molecules 1–24 were evaluated for their in vitro antioxidant activity and compared with commercial antioxidants ascorbic acid (AA) and gallic acid (GA), employing 1,1-diphenyl-2-picryl-hydrazyl (DPPH), N,N-dimethyl-p-phenylenediamine dihydrochloride (DMPD) and 2,2-azinobis-(3-ethylbenzothiazoline-6-sufonic acid) (ABTS) assays. The results revealed that IC50 of 8, 11, 20 and 23 with electron donating OCH3 group were lower than the IC50 of commercial standards AA and GA in all the three performed antioxidant assays indicating the good activities of these compounds. The analogues with Trp (13–24) showed better activity than the corresponding analogues with Asp (1–12). Further, the dipeptide derivatives with d-configuration (lys) were found to be more potent than the dipeptide derivatives with l-configuration (Lys).
KeywordsConjugation Bisthiourea Antioxidant Dipeptides Configuration
The authors gratefully acknowledge Department of Science and Technology (DST) New Delhi for awarding Inspire Fellowship, University Grant Commission (UGC) New Delhi for awarding BSR faculty fellowship, DST-Purse and Instrumentation facility.
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Conflict of Interest
The authors have no conflict of interest regarding the publication of this paper.
The authors declare that there were no animals or humans involved in this study as subjects.
- Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Ferrnandez-Luna JL, Nunez G (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 278:5509–5512CrossRefPubMedGoogle Scholar
- Kastin A (2013) Handbook of biologically active peptides. Acadamic press, LondonGoogle Scholar
- Saeed S, Rashid N, Jones PG, Hussain R, Bhatti MH (2010b) Synthesis, spectroscopic characterization, crystal structure and antifungal activity of thiourea derivatives containing a thiazole moiety. Cent Eur J Med Chem 8:550–558Google Scholar
- Schulman JR, Keating RP (1950) Studies on the metabolism of thiourea. Distribution and excretion in the rat of thiourea labeled with radioactive sulfur. J Biol Chem 183:215–221Google Scholar
- Sobha RI, Andallu B (2013) Oxidative stress and cancer: role of anticarcinogenic herbs and species. AJPCT 3:351–369Google Scholar
- Suyoga Vardhan DM, Shantharam CS, Suhas R, Sridhara MB, Channe Gowda D (2013) Synthesis and structure activity relationship studies of urea and thiourea derivatives of glycine/proline conjugated to 2,3-dichlorophenyl piperazine: an effective class of AGE inhibitors. Protein Pept Lett 20:888–897CrossRefGoogle Scholar
- Yonova P, Guleva E (1997) Plant growth regulating activity of some novel 1,1-polymethylenebis(3-arylsubstituted)thioureas. Bulg J Plant Physiol 23:72–79Google Scholar