Synthesis, Structural Studies, and α-Glucosidase Inhibitory, Antidiabetic, and Antioxidant Activities of 2,3-Dihydroquinazolin-4(1H)-ones Derived from Pyrazol-4-carbaldehyde and Anilines

Abstract

A series of new quinazoline derivatives were designed and synthesized via a one-pot condensation reaction between isatoic anhydride and aromatic aldehydes with anilines using aluminum sulfate as a catalyst in refluxing ethanol. Their structures were confirmed by their physical, IR, 1H NMR, 13C NMR, and mass spectroscopy data and evaluated for some biological effects, including the antioxidant and α-glucosidase inhibitory activities as well as some in vivo hematological parameters. The ability of synthesized compounds in the inhibition of α-glucosidase was also investigated through the in silico study. The significant and important changes in some hematological tests were perceived. Notably, compound 4h showed more reducing effects on cholesterol and triglyceride levels. This molecule certainly has the potential to be developed as the antihyperlipemic compound. The tested compounds, in particular, compounds 4j and 4l, were found to be uniquely reducing blood sugar levels. The entire synthesized compounds showed the potent α-glucosidase inhibitory activity compared with acarbose as a standard material. Amongst, the compounds 4h and 4i showed the strongest enzyme inhibitory potentials than the standard drug acarbose. There was a good correlation between in vitro and in silico studies for ligands 4i and 4l. The majority of compounds presented a good radical scavenging activity, though the compound 4j exhibited the strongest activity, even to the standard of ascorbic acid. Further studies are required to determine whether these main compounds could be a potential treatment for diabetes and hyperlipidemia diseases.

Design and Synthesis of Fluoroquinolone Derivatives as Potent α‐Glucosidase Inhibitors: In Vitro Inhibitory Screening with In Silico Docking Studies

“…Results shows that all compounds 1 – 10 are excellent inhibitors of α‐glucosidase with IC 50 in the range of 45.8–74.5 μ M compared to standard 1‐deoxynojirimycin (DNJ) with an IC 50 value of 425.6 μ M. Study reveals that precursor enoxacin exhibit and IC 50 value of 58.9 μ M while substitution of benzyl group as in compound 1 increases the inhibition potential to a small extent with an IC 50 value of 57.8 μ M. Substitution of chloro at meta and para position as in molecules 5 , bromo at ortho 6 and fluoro at ortho and para position 8 on benzyl further increased the inhibition potentials IC 50 values 52.7, 45.8 and 48.7 μ M. Whereas compounds 2 , 3 , 4 , 7 , 9 and 10 were found to have higher IC 50 values in the range of 59.8‐74.5 μ M. Compound 6 was found to be a most potent inhibitor of α ‐glucosidase with an IC 50 value 45.8 μ M. Studies found that position and nature of substituent group shows effect on inhibition potential [40–43] . It is suggested that little variation in hydrogen bonding between protein active sites and synthetic compounds are responsible for variation in inhibition potential of these compounds against α ‐glucosidase [44–46] .…”

Synthesis, X-ray Structure, Hirshfeld, DFT and Biological Studies on a Quinazolinone-Nitrate Complex

“…Quinazolines have a broad range of pharmacological applications, in addition to their low toxicity profiles [ 3 ]. Quinazoline frameworks have great pharmacological activities as antioxidant [ 7 , 8 , 9 ], antidiabetic [ 10 , 11 , 12 ], antibacterial [ 13 , 14 , 15 ], antiviral [ 16 , 17 , 18 ], antimicrobial [ 19 , 20 , 21 ], anticancer [ 22 , 23 ], antihistaminic [ 24 , 25 , 26 ], antidiuretic [ 27 , 28 ], antitubercular [ 29 , 30 , 31 ], and anti-inflammatory [ 32 , 33 , 34 ] agents. Quinazolinones are a type of quinazoline derivative that are biologically active in the same way as quinazoline [ 35 ].…”

Review on the Significance of Quinazolinone Derivatives as Potent Antihyperglycemic Agents

“…In most cases, the prescribed antidiabetic drugs are responsible for various side effects such as liver problems, diarrhea, lactic acidosis, and high rate of secondary failure. So that, the discovery of novel small molecules with potential usefulness as potent hypoglycemic agents is still a major challenge to medicinal chemistry researchers (Barmak, Niknam et al 2019).…”