article · RSC Advances
A new series of sulfonamide derivatives featuring five- or seven-membered heterocycles linked by an imine group has been designed, synthesised, and structurally confirmed. Laboratory testing demonstrated that several derivatives effectively inhibit alpha-glucosidase, with compounds 3a, 3b, 3h, and 6 exhibiting higher potency than the standard drug acarbose. Additionally, compounds 3g, 3i, and 7 significantly enhanced glucose uptake, showing up to twenty-seven times greater potency than berberine. Molecular docking investigations indicated that the most active derivatives bind into the alpha-glucosidase active site similarly to acarbose, while displaying weaker interactions with alpha-amylase, which explains their selective enzymatic inhibition. Furthermore, computational analysis revealed that the physicochemical properties of all synthesised compounds conform to Lipinski's rule of five, indicating favourable drug-like profiles.
Managing blood sugar levels is central to treating diabetes, but existing medications can have limitations in efficacy or selectivity. By presenting compounds that combine dual benefits, enzyme inhibition and enhanced glucose uptake, alongside favourable drug-like properties, this research highlights promising chemical frameworks for developing potentially more effective therapeutic candidates to control diabetes.
This work is at an early laboratory stage of drug discovery, having demonstrated activity through in vitro assays and molecular docking. The findings could interest pharmaceutical and biotechnology companies developing oral antidiabetic therapeutics. Significant further development, including extensive cellular toxicity testing, in vivo pharmacokinetic evaluations, and formal safety studies, will be required before these compounds could advance toward clinical application.
AI-generated from the published abstract. Always read the original work before citing.
A series of new sulfonamide derivatives connected through an imine linker to five or seven membered heterocycles were designed and synthesized. All synthesized derivatives were characterized using a variety of spectroscopic methods, including IR, <sup>1</sup>HNMR, and <sup>13</sup>CNMR. <i>In vitro</i> α-glucosidase and α-amylase inhibition activities, as well as glucose uptake were assessed for each of the synthesized compounds. Four sulfonamide derivatives namely 3a, 3b, 3h and 6 showed excellent inhibitory potential against α-glucosidase with IC<sub>50</sub> values of 19.39, 25.12, 25.57 and 22.02 μM, respectively. They were 1.05- to 1.39-fold more potent than acarbose. Sulfonamide derivatives 3g, 3i and 7 (EC<sub>50</sub> values of 1.29, 21.38 and 19.03 μM, respectively) exhibited significant glucose uptake activity that were 1.62- to 27-fold more potent than berberine. Both α-glucosidase protein (PDB: 2QMJ) and α-amylase (PDB: 1XCW) complexed with acarbose were adopted for docking investigations for the most active synthesized compounds. The docked compounds were able to inhabit the same space as the acarviosin ring of acarbose. The docking of the most active compounds showed an analogous binding with the active site of α-glucosidase as acarbose. The superior activity of the synthesized compounds against α-glucosidase enzyme than α-amylase enzyme can be rationalized by the weak interaction with the α-amylase. The physiochemical parameters of all synthesized compounds were aligned with Lipinski's rule of five.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.1039/d4ra01060d
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
