Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents

H Chen; YB Ma; XY Huang; CA Geng; Yong Zhao; LJ Wang; RH Guo; XM Zhang; JJ Chen

doi:10.1016/j.bmcl.2014.03.060

Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents

H Chen, YB Ma, XY Huang, CA Geng, Yong Zhao, LJ Wang, RH Guo, XM Zhang, JJ Chen

58 Citations (Scopus)

Abstract

Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC₅₀ values of 22.58 and 54.07 μM and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal log P value of 1.78 and log D values. Structure-activity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs.

Original language	English
Journal	Biooganic & Medicinal Chemistry Letters
Volume	24
Issue number	10
Pages (from-to)	2353-2359
DOIs	https://doi.org/10.1016/j.bmcl.2014.03.060
Publication status	Published - 15 May 2014
Externally published	Yes

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Chen, H., Ma, YB., Huang, XY., Geng, CA., Zhao, Y., Wang, LJ., Guo, RH., Zhang, XM., & Chen, JJ. (2014). Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents. Biooganic & Medicinal Chemistry Letters, 24(10), 2353-2359 . https://doi.org/10.1016/j.bmcl.2014.03.060

Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents. / Chen, H; Ma, YB; Huang, XY et al.
In: Biooganic & Medicinal Chemistry Letters, Vol. 24, No. 10, 15.05.2014, p. 2353-2359 .

Research output: Contribution to journal › Journal article › Research › peer-review

Chen, H, Ma, YB, Huang, XY, Geng, CA, Zhao, Y, Wang, LJ, Guo, RH, Zhang, XM & Chen, JJ 2014, 'Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents', Biooganic & Medicinal Chemistry Letters, vol. 24, no. 10, pp. 2353-2359 . https://doi.org/10.1016/j.bmcl.2014.03.060

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title = "Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents",

abstract = "Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07 μM and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal log P value of 1.78 and log D values. Structure-activity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs.",

author = "H Chen and YB Ma and XY Huang and CA Geng and Yong Zhao and LJ Wang and RH Guo and XM Zhang and JJ Chen",

year = "2014",

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doi = "10.1016/j.bmcl.2014.03.060",

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AU - Chen, H

AU - Ma, YB

AU - Huang, XY

AU - Geng, CA

AU - Zhao, Yong

AU - Wang, LJ

AU - Guo, RH

AU - Zhang, XM

AU - Chen, JJ

PY - 2014/5/15

Y1 - 2014/5/15

N2 - Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07 μM and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal log P value of 1.78 and log D values. Structure-activity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs.

AB - Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07 μM and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal log P value of 1.78 and log D values. Structure-activity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs.

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DO - 10.1016/j.bmcl.2014.03.060

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JO - Biooganic & Medicinal Chemistry Letters

JF - Biooganic & Medicinal Chemistry Letters

IS - 10

ER -

Synthesis, Structure-activity relationships and biological evaluation of dehydro-andrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents

Abstract

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