Synthesis and biological evaluation of 2‐acylbenzofuranes as novel α‐glucosidase inhibitors with hypoglycemic activity

Abstract

A series of benzofuran derivatives was synthesized as analogues of known natural α-glucosidase inhibitors. Their activity was evaluated in enzymatic assay and in rat model of diabetes mellitus. Newly identified inhibitors demonstrate significant potency with IC values ranging from 6.50 to 722.2 μm, as well as hypoglycemic activity exceeding the reference drug acarbose. Docking simulations provided insight into structure-activity relationships to direct further development of these novel hypoglycemic agents.

Dihydronaphthofurans: synthetic strategies and applications

“…In a similar manner, 2-aryl-1,2-dihydronaphtho[2,1-b]furans 149 in 29-45% yields were synthesized by the reaction of 2naphthol Mannich base and pyridinium salts 150 in reuxing DMF for 5 h under an argon atmosphere (Scheme 69). 62 Spasov et al 12 ) could also be obtained in 50% yield from the Mannich base methiodide of 2-naphthol via the corresponding quinone methide in the presence of dimethyl sulfoxonium methylide in dimethyl sulfoxide (DMSO) and base (B ¼ Na + -CH 2 SOCH 3 ) (Scheme 71). 63 In a similar manner, dihydronaphthofuran 11b was obtained by the reaction of Mannich bases, Mannich base methiodides, and Mannich base N-oxides derived from naphthols with diazomethane in CH 2 Cl 2 at 3 C for 16-96 h or with dimethylsulphoxonium methylide in DMSO at 20-100 C for 2-48 h in 0-28% yields (Scheme 72).…”

“…They have demonstrated signicant potency with IC 50 values ranging from 6.50 to 722.2 mM, as well as hypoglycemic activity exceeding the reference drug acarbose. 12…”

“…Furthermore, some of the synthesized dihydronaphthofuran derivatives exhibit a variety of interesting biological and pharmacological properties including 5-lipoxygenase inhibitor, 7 C 17,20 lyase inhibitors, 8 antitubercular activity against Mycobacterium tuberculosis H 37 Rv, 9 anti-tyrosinase, antioxidant, and antibacterial, 10 inhibitors of NFk B activity, 11 a-glucosidase inhibitors, 12 inhibitor of a-chymotrypsin 13 and anti cancer activities (liver tumor growth inhibitors). 14 Moreover, vinylidene-naphthofurans are a new class of polycyclic compounds that exhibit photochromic properties when exposed to the UV or sunlight at room temperature and adsorbed in silica gel or dissolved in acidied alcoholic solutions (Fig.…”

Synthesis, In Vitro Evaluation and Molecular Docking of the 5-Acetyl-2-aryl-6-hydroxybenzo[b]furans against Multiple Targets Linked to Type 2 Diabetes

“…The naturally occurring 2,4-dihydroxy-5-methylacetophenone and its derivatives have been found to exhibit α-glucosidase inhibitory properties [19]. Likewise, the 2-acylbenzofurans were found to inhibit α-glucosidase and to exhibit hypoglycaemic activity [20]. The analogous 2-unsubstituted 5-acetyl-4-hydroxybenzofurans and 5-acetyl-6-hydroxybenzofurans as well as their benzoylated derivatives, on the other hand, exhibit an inhibitory effect against PTP1B activity [21].…”

Synthesis, structure and in vitro cytotoxicity testing of some 2-aroylbenzofuran-3-ols

“…Some synthetic benzofuran derivatives have been investigated in the role of osteogenic (Marquè s et al, 2016;Kushwaha et al, 2018;Modukuri et al, 2017) or vasorelaxant (Hassan et al, 2014) agents. 2-Aroylbenzofuran-3-ols, being a class of typical benzofuran derivatives, not only possess antimicrobial (Kulkarni et al, 2014), antitumour (Sargolzaei et al, 2016) andglucosidase inhibition (Spasov et al, 2017) properties, but are also useful intermediates for the synthesis of several compounds having various biological activities (Shi et al, 2016;Dong et al, 2013;Rashmi et al, 2015). Although many 2-aroylbenzofuran-3-ols have been synthesized and studied for their biological activities, the structural characteristics and cytotoxic activity of 2-aroyl-5-bromobenzo [b]furan-3-ol and 2-aroyl-5-iodobenzo [b]furan-3-ol compounds have not been studied much.…”