Synthesis and in Silico Studies of a Benzenesulfonyl Curcumin Analogue as a New Anti Dengue Virus Type 2 (DEN2) NS2B/NS3

Ihsan Ikhtiarudin

doi:10.14499/indonesianjpharm30iss2pp84-90

Abstract

Curcumin has been reported can interact with multiple molecular targets involved in a large variety of diseases. Accumulated evidence indicated curcumin plays an inhibitory role against infection of numerous viruses. Some studies have been reported that curcumin can interfere the infection processes of dengue virus. In this work, a benzenesulfonyl curcumin, (3 E ,5 E )-3,5-bis(4-methoxybenzylidene)-1-(phenylsulfonyl)piperidin-4-one (compound 2 ) has been synthesized by two steps of reactions. The structure of compound 2 has been established based on the interpretation of spectral data include UV, FT-IR, MS/MS, 1 H and 13 C NMR. Then, the in silico studies have been also performed to predict the potency of compound 2 as inhibitor for dengue virus Type 2 (DEN 2) NS2B/NS3 protease. The in silico studies showed that compound 2 has hydrogen bonding with His51 residue, and amazingly that the other catalytic triad such as Asp75 and Ser135 were also showed interactions with the ligand. It is presumably that this compound showed very good activity against DEN2 and can be developed as a new inhibitor for dengue viruses.

Highlights

Dengue is the most rapidly spreading disease caused by a mosquito-borne virus in the word
A number of studies have already revealed that the non-structural 3 (NS3) serine protease is required for the maturation of the viral polyprotein
The binding of the NS3 serine protease to an NS2B cofactor will form NS2B-NS3 protease complex (Chambers et al, 1993) which is required to cleave the viral precursor proteins that is required for dengue virus type 2 (DEN2) viral replication (Falgout et al, 1991)

Summary

INTRODUCTION

Dengue is the most rapidly spreading disease caused by a mosquito-borne virus in the word. The binding of the NS3 serine protease to an NS2B cofactor will form NS2B-NS3 protease complex (Chambers et al, 1993) which is required to cleave the viral precursor proteins that is required for DEN2 viral replication (Falgout et al, 1991). It is a promising target for the development of dengue antiviral drugs (Sampath and Padmanabhan, 2009).

MATERIAL AND METHODS

AND DISCUSSION

CONCLUSION

2011. Design of new competitive dengue