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CC BY-ND-NC 4.0 · SynOpen 2018; 02(02): 0200-0206
DOI: 10.1055/s-0036-1591967
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Microwave-Assisted Synthesis of Andrographolide Analogues as Potent β-Glycosidase Inhibitors

Masood ur Rahman
a   Organic Chemistry Research Lab, Department of Chemistry, National Institute of Technology, Srinagar, 190006, India
b   Bioorganic Chemistry Division, IIIM, Sanatnagar, Srinagar, 190005, India
,
Iram Ayoob
c   Department of Chemistry, University of Kashmir, Srinagar, 190006, India
,
Shakeel u Rehman
c   Department of Chemistry, University of Kashmir, Srinagar, 190006, India
,
Khursheed A. Bhat
b   Bioorganic Chemistry Division, IIIM, Sanatnagar, Srinagar, 190005, India
,
Tabassum Ara*
a   Organic Chemistry Research Lab, Department of Chemistry, National Institute of Technology, Srinagar, 190006, India
› Author AffiliationsM.R. is grateful to MHRD for providing a research fellowship
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Publication History

Received: 31 December 2017

Accepted after revision: 04 March 2018

Publication Date:
13 June 2018 (online)

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Abstract

Andrographolide, a bioactive compound isolated from Andrographis paniculata exhibits multiple pharmacological activities, including anti-HIV, antiplatelet aggregation, hepatic lipid peroxidation protective, hepatoprotective, choleretic, and anticancer effects. Herein, we report the synthesis of diverse analogues of andrographolide along with their β-glucosidase inhibitory activity against sweet almond β-glucosidase. The parent compound, And-1, displayed moderate inhibitory activity against the sweet almond β-glucosidase with IC50 of 142.5 μM. Among the synthesised analogues And-10 showed the best activity, with IC50 of 92.4 μM, whereas the oxidised products (And-4 and And-5) were moderately active against the tested enzyme. Additionally, compounds And-6, And-7, And-8, and And-10 exhibited better β-glucosidase inhibitory activity than the positive control Castanospermine, with IC50 of 100.2, 102.4, 106.5, and 92.4 μM, respectively. These results highlight the importance of an electron-withdrawing NO2 group on the phenyl moiety in attaining the better β-glucosidase inhibition. It is noteworthy that the effect of a particular group plays a significant role in bioactivity. This study thus highlights an important aspect with regard to the most active compounds, which could extend the arsenal of compounds affecting the corresponding enzymes after further polishing and fine tuning.

Key words

andrographolide - β-glucosidase - sweet almond - Castanospermine

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    Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591967.
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