Synthesis of arylated tetrahydrobenzo[]quinoline-3-carbonitrile derivatives as potential hits for treatment of diabetes.

Quinoline scaffolds are serving as the core structure for numerous antifungal, analgesic, antipyretic, anti-inflammatory drugs as well as have also been investigated for their potential antidiabetic properties. Though further exploration is required in this area as the current antidiabetic agents, such as acarbose, miglitol and voglibose, are associated with several adverse side effects. In this context, arylated tetrahydrobenzo[]quinoline-3-carbonitrile derivatives were designed and evaluated as potential antidiabetic agents.

Exploration of thiazine Schiff bases as promising urease inhibitors: Design, synthesis, enzyme inhibition, kinetic analysis, ADME/T evaluation, and molecular docking studies.

Urease catalyzes the hydrolysis of urea, leading to an increase in stomach pH and supporting Helicobacter pylori survival, which is linked to several gastrointestinal disorders. In this study, thiazine-based Schiff bases were explored as promising urease inhibitors. Various spectroscopic techniques characterized the synthetic library of thiazine Schiff bases 2-36 and also evaluated for their inhibitory activities against urease.

Coumarin derivatives as new anti-biofilm agents against Staphylococcus aureus.

Staphylococcus aureus infections are the primary causes of morbidity, and mortality, particularly in immuno-compromised individuals. S. aureus associated infections are acquired from community, as well as hospital settings, and difficult to treat because of the emerging resistance against available antibiotics.

Imidazole-thiadiazole hybrids: A multitarget de novo drug design approach, in vitro evaluation, ADME/T, and in silico studies.

A library of imidazole-thiadiazole compounds (1-24) was synthesized to explore their therapeutic applications. The compounds were subjected to meticulous in vitro evaluation against α-glucosidase, α-amylase, acetylcholinesterase (AChE), and butylcholinesterase (BChE) enzymes. Compounds were also investigated for antioxidant activities using cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays.

Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers.

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC values of 11.01-56.

Biochemical evaluation and ligand binding studies on glycerophosphodiester phosphodiesterase from Staphylococcus aureus using STD-NMR spectroscopy and molecular docking analysis.

Glycerophosphodiester phosphodiesterase (GDPD) is a highly conserved enzyme in both prokaryotic and eukaryotic organisms. It catalyses the hydrolysis of various glycerophosphodiesters into glycerol-3-phosphate and corresponding alcohols, which serve as building blocks in several biosynthetic pathways. This enzyme is a well-known virulence factor in many pathogenic bacteria, including Staphylococcus aureus, and is thus considered a potential drug target.

Indenoquinoxaline-phenylacrylohydrazide hybrids as promising drug candidates for the treatment of type 2 diabetes: In vitro and in silico evaluation of enzyme inhibition and antioxidant activity.

Existing drugs that are being used to treat type-2 diabetes mellitus are associated with several side effects; thus, exploring potential drug candidates is still an utter need these days. Hybrids of indenoquinoxaline and hydrazide have never been explored as antidiabetic agents. In this study, a series of new indenoquinoxaline-phenylacrylohydrazide hybrids (1-30) were synthesized, structurally characterized, and evaluated for α-amylase and α-glucosidase inhibitory activities, as well as for their antioxidant properties.

Synthesis of new (dimethylamino)benzophenone hydrazone for diabetic management: and approach.

Inhibiting α-glucosidase is a reliable method for reducing blood sugar levels in diabetic individuals. (dimethylamino)benzophenone derivatives - were synthesized from (dimethylamino)benzophenone via two-step reaction. Different spectroscopic techniques, including EI-MS and 1H NMR, were employed to characterize all synthetic derivatives.

Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus.

Diabetes mellitus is a significant health disorder; therefore, researchers should focus on discovering new drug candidates. A series of indole-pyridine carbonitrile derivatives, , were synthesized through a one-pot multicomponent reaction and evaluated for antidiabetic and antioxidant potential. In this library, 12 derivatives - , , , , , , , , and - exhibited potent inhibitory activities against α-glucosidase and α-amylase enzymes, in comparison to acarbose (IC = 14.

Determining the 3-substituted Coumarins inhibitory potential against the HslV protease of E. coli.

Objective: The growing bacterial resistance towards classical antibiotics demands the development of novel approaches for the effective treatment of potentially fatal bacterial infections in humans. Proteostasis is crucial for the survival of every living cell, as several important physiological functions depend on well-regulated proteostasis. Within bacteria, the regulation of proteostasis relies on AAA+ (Adenosine 5'-triphosphatases associated with diverse cellular activities), ATPases, such as the HslVU complex (heat shock locus gene products U and V), along with other proteases.

Evaluation of synthetic aminoquinoline derivatives as urease inhibitors: , and kinetic studies.

Quinoline and acyl thiourea scaffolds have major chemical significance in medicinal chemistry. Quinoline-based acyl thiourea derivatives may potentially target the urease enzyme. Quinoline-based acyl thiourea derivatives - were synthesized and tested for urease inhibitory activity.

Multitargeted inhibition of key enzymes associated with diabetes and Alzheimer's disease by 1,3,4-oxadiazole derivatives: Synthesis, in vitro screening, and computational studies.

A library of 22 derivatives of 1,3,4-oxadiazole-2-thiol was synthesized, structurally characterized, and assessed for its potential to inhibit α-amylase, α-glucosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and antioxidant activities. Most of the tested compounds demonstrated good to moderate inhibition potential; however, their activity was lower than that of the standard acarbose. Significantly, compound 3f exhibited the highest inhibition potential against α-glucosidase and α-amylase enzymes, with IC values of 18.

Diphenyl-substituted triazine derivatives: synthesis, α-glucosidase inhibitory activity, kinetics and studies.

Diabetes mellitus (DM) is a chronic disorder, considered to be a major global health challenge in the 21st century. α-Glucosidase enzyme is a well-known drug target to treat Type II DM. A new library of biphenyl-substituted triazines was synthesized and confirmed by various spectroscopic techniques.

Multicomponent diastereoselective synthesis of tetrahydropyridines as α-amylase and α-glucosidase enzymes inhibitors.

Researchers seeking new drug candidates to treat diabetes mellitus have been exploring bioactive molecules found in nature, particularly tetrahydropyridines (THPs). A library of THPs () were synthesized via a one-pot multicomponent reaction and investigated for their inhibition potential against α-glucosidase and α-amylase enzymes. A nitrophenyl-substituted compound with IC values of 0.

Regioselective syntheses of 2-oxopyridine carbonitrile derivatives and evaluation for antihyperglycemic and antioxidant potential.

A library of 2-oxopyridine carbonitriles 1-34 was synthesized by regioselective nucleophilic substitution reactions. In the first step, a one-pot multicomponent reaction yield pyridone intermediates. The resulting pyridone intermediates were then reacted with phenacyl halides in DMF and stirred at 100 °C for an hour to afford the desired compounds in good yields.

Synthetic piperidine-substituted chalcones as potential hits for α-amylase inhibitory and antioxidant activities.

In medicinal chemistry, searching for new therapeutic entities to treat diabetes mellitus is of great concern. The piperidinyl-substituted chalcone scaffold has piqued our interest as a potential antidiabetic agent. A variety of piperidinyl-substituted chalcones were synthesized and tested for α-amylase inhibitory and 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-(3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activities.

Synthetic benzofuran-linked chalcones with dual actions: a potential therapeutic approach to manage diabetes mellitus.

Identification of molecules having dual capabilities to reduce postprandial hyperglycemia and oxidative stress is one of the therapeutic approaches to treat diabetes mellitus. In this connection, a library of benzofuran-linked chalcone derivatives were evaluated for their dual action. A series of substituted benzofuran-linked chalcones () were synthesized and tested for α-amylase inhibitory as well as 2,2-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities.

Design, synthesis and bio-evaluation of indolin-2-ones as potential antidiabetic agents.

Diabetes mellitus is a serious global health concern, and this is expected to impact more than 300 million people by 2025. The current study focuses on identifying substituted indolin-2-one-based inhibitors for two indispensable drug targets, α-amylase and α-glucosidase. The structures of synthetic compounds were confirmed by spectroscopic techniques and evaluated for enzyme inhibition activities.

Author Correction: Inhibitory potential of triazines and hydrazinyl thiazole substituted chromones against the HslVU protease/chaperone complex, a novel drug target.

Correction to: European Review for Medical and Pharmacological Sciences 2022; 26 (22): 8567-8575. DOI: 10.26355/eurrev_202211_30392-PMID: 36459037-published online on November 30, 2022.

Inhibitory potential of triazines and hydrazinyl thiazole substituted chromones against the HslVU protease/chaperone complex, a novel drug target.

Objective: Proteostasis is an important process occurring in all living cells and is highly indispensable for cell survival. The HslVU protease/chaperone complex's critical role in regulating proteostasis to maintain a healthy cellular proteome and its presence in pathogenic microbes made it an important drug target. This study aimed to identify small molecular inhibitors of the HslV protease.

Bioevaluation of synthetic pyridones as dual inhibitors of α-amylase and α-glucosidase enzymes and potential antioxidants.

Herein, a library of novel pyridone derivatives 1-34 was designed, synthesized, and evaluated for α-amylase and α-glucosidase inhibitory as well as antioxidant activities. Pyridone derivatives 1-34 were synthesized via a one-pot multi-component reaction of variously substituted aromatic aldehydes, acetophenone, ethyl cyanoacetate, and ammonium acetate in absolute ethanol. Synthetic compounds 1-34 were structurally characterized by different spectroscopic techniques.

Efficient one-pot synthesis of arylated pyrazole-fused pyran analogs: as leads to treating diabetes and Alzheimer's disease.

To discover novel lead molecules against diabetes, Alzheimer's disease and oxidative stress, a library of arylated pyrazole-fused pyran derivatives, , were synthesized in a one-pot reaction. H-NMR spectroscopic and electron ionization mass spectrometry techniques were used to characterize the synthetic hybrid molecules . Analogs were screened against four indispensable therapeutic targets, including -amylase, -glucosidase, acetylcholinesterase and butyrylcholinesterase enzymes.

3-substituted coumarin derivatives over-activate the HslV protease: A potential drug target for antibacterial activity.

The bacterial HslVU complex consists of two different proteins, i.e., the HslV protease and the HslU ATPase.

Hydrazinyl thiazole linked indenoquinoxaline hybrids: Potential leads to treat hyperglycemia and oxidative stress; Multistep synthesis, α-amylase, α-glucosidase inhibitory and antioxidant activities.

A library of hydrazinyl thiazole-linked indenoquinoxaline hybrids 1-36 were synthesized via a multistep reaction scheme. All synthesized compounds were characterized by various spectroscopic techniques including EI-MS (electron ionization mass spectrometry) and H NMR (nuclear magnetic resonance spectroscopy). Compounds 1-36 were evaluated for their inhibitory potential against α-amylase, and α-glucosidase enzymes.