Design, synthesis and in vivo screening of some novel quinazoline analogs as anti-hyperlipidemic and hypoglycemic agents

Mokale, Santosh N.; Palkar, Akash D.; Dube, Pritam N.; Sakle, Nikhil S.; Miniyar, Pankaj B.

doi:10.1016/j.bmcl.2015.12.037

Cited by 16 publications

(5 citation statements)

References 11 publications

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“…[ 29,30 ] Furthermore, the fibrate‐quinazolinone hybrid X (Figure 1) has proven its efficacy as a lipid‐lowering agent by reducing the levels of TC, TG, LDL‐c, and elevating HDL‐c level in the hypercholesterolemic model. [ 31 ] Moreover, various quinazolinone derivatives displayed significant antioxidant activity, [ 32,33 ] such as compound XI (Figure 1), which achieved an alleviation of gamma radiation‐induced oxidative stress in mice by reducing the levels of liver malondialdehyde (MDA) and reactive oxygen species (ROS). [ 34 ]…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of novel quinazolinone‐based fibrates as PPARα agonists with antihyperlipidemic activity

Hassan

Ali

Abdel‐Maksoud

et al. 2021

Archiv der Pharmazie

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Aiming to discover new antihyperlipidemic agents, a new set of quinazolinone‐fibrate hybrids 9a–r bearing the essential features for peroxisome proliferator‐activated receptor‐α (PPARα) agonistic activity was synthesized and the structures were confirmed by different spectral data. All the target compounds were screened for their PPARα agonistic activity. Compounds 9o and 9q exhibited potent activity, with EC50 values better than that of fenofibrate by 8.7‐ and 27‐fold, respectively. Molecular docking investigations were performed for all the newly synthesized compounds in the active site of the PPARα receptor to study their interactions and energies in the receptor. Moreover, the antihyperlipidemic and antioxidant activities of compounds 9o and 9q were determined using Triton WR‐1339‐induced hyperlipidemic rats. Compound 9q exhibited effective hypolipidemic activity in a dose‐dependent manner, where it significantly reduced the serum levels of total cholesterol, triglycerides, low‐density lipoprotein cholesterol, and very‐low‐density lipoprotein cholesterol and increased the level of high‐density lipoprotein cholesterol. Furthermore, it possesses a powerful antioxidant profile where it significantly elevated the levels of reduced glutathione as well as the total antioxidant capacity and significantly decreased the malondialdehyde level. The histopathological studies revealed that compound 9q improved the aortic architecture and hepatic steatosis. These findings support that compound 9q could be a promising lead compound for the development of new antihyperlipidemic agents.

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Section: Introductionmentioning

confidence: 99%

Design and synthesis of novel quinazolinone‐based fibrates as PPARα agonists with antihyperlipidemic activity

Hassan

Ali

Abdel‐Maksoud

et al. 2021

Archiv der Pharmazie

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“…In this work, we report the optimization of the reduction process of 1,2,4-oxadiazoles to directly obtain amidine and guanidine as well as quinazolin-4-ones through a reduction-induced heterocyclic rearrangement. All these compounds are of great interest due to their potential biological activity [24][25][26][27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

“…rearrangement. All these compounds are of great interest due to their potential biological activity [24][25][26][27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity

Marzullo

Vasto

Buscemi

et al. 2021

IJMS

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1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4CO2H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2′-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics.

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“…Therefore, much effort has been undertaken to search for more effective and safer inhibitors. Recently, new effective and safer inhibitors from natural products and their derivatives have continued [8,9]. Many flavonoids have shown some considerable inhibitory effects against α-glucosidase enzymes, such as morin [10], luteolin [11], baicalein [12], kaempferol [13] and apigenin [7].…”

Section: Introductionmentioning

confidence: 99%

Effects of Hydroxyl Group on the Interaction of Carboxylated Flavonoid Derivatives with S. Cerevisiae α-Glucosidase

Zhao

et al. 2020

CAD

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Introduction: Carboxyalkyl flavonoids derivatives are considered as effective inhibitors in reducing post-prandial hyperglycaemia. Methods: Combined with Density Functional Theory (DFT) and the theory of Atoms in Molecules (AIM), molecular docking and charge density analysis are carried out to understand the molecular flexibility, charge density distribution and the electrostatic properties of these carboxyalkyl derivatives. Results: Results show that the electron density of the chemical bond C14-O17 on B ring of molecule II increases while O17-H18 decreases at the active site, suggesting the existence of weak noncovalent interactions, most prominent of which are H-bonding and electrostatic interaction. When hydroxyl groups are introduced, the highest positive electrostatic potentials are distributed near the B ring hydroxyl hydrogen atom and the carboxyl hydrogen atom on the A ring. It was reported that quercetin has a considerably inhibitory activity to S. cerevisiae α-glucosidase, from the binding affinities, it is suggested that the position and number of hydroxyl groups on the B and C rings are also pivotal to the hypoglycemic activity when the long carboxyalkyl group is introduced into the A ring. Conclusion: It is concluded that the presence of three well-defined zones in the structure, both hydrophobicity alkyl, hydrophilicity carboxyl and hydroxyl groups are necessary.

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Design, synthesis and in vivo screening of some novel quinazoline analogs as anti-hyperlipidemic and hypoglycemic agents

Cited by 16 publications

References 11 publications

Design and synthesis of novel quinazolinone‐based fibrates as PPARα agonists with antihyperlipidemic activity

Design and synthesis of novel quinazolinone‐based fibrates as PPARα agonists with antihyperlipidemic activity

Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity

Effects of Hydroxyl Group on the Interaction of Carboxylated Flavonoid Derivatives with S. Cerevisiae α-Glucosidase

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