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Synthesis and SAR Studies of Bisthiourea Derivatives of Dipeptides Lys/lys-Asp, Lys/lys-Trp Conjugated Benzo[d]isoxazole as Promising Antioxidants

  • H. K. Kumara
  • D. Channe Gowda
Article

Abstract

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).

Keywords

Conjugation Bisthiourea Antioxidant Dipeptides Configuration 

Abbreviations

Boc

t-Butyloxycarbonyl

HOBt

1-Hydroxybenzotriazole

EDCI

1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide.HCl

NMM

N-methyl morpholine

TFA

Trifluroacetic acid

IBCF

Isobutyl chloroformate

Lys

d-Lysine

Notes

Acknowledgments

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.

Compliance with Ethical Standards

Conflict of Interest

The authors have no conflict of interest regarding the publication of this paper.

Ethical Approval

The authors declare that there were no animals or humans involved in this study as subjects.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Studies in ChemistryUniversity of MysoreMysuruIndia

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