Design, synthesis and in vitro α-glucosidase inhibition of novel dihydropyrano[3,2-c]quinoline derivatives as potential anti-diabetic agents

Nikookar, Hamideh; Mohammadi-Khanaposhtani, Maryam; Imanparast, Somaye; Faramarzi, Mohammad Ali; Ranjbar, Parviz Rashidi; Mahdavi, Mohammad; Larijani, Bagher

doi:10.1016/j.bioorg.2018.01.025

Cited by 80 publications

(35 citation statements)

References 21 publications

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“…DMSO (10% final concentration) and acarbose were used respectively as control and standard drug. The percentage of enzyme inhibitionwas calculated and IC 50 values were obtained from non-linear regression curve using the Logit method 84 .…”

Section: Methodsmentioning

confidence: 99%

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Peytam

Adib

Shourgeshty

et al. 2020

Sci Rep

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In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC 50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC 50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. Recently, the world health organization (WHO) has identified the diabetes mellitus (DM) as a critical health challenge in the 21st century. The prevalence of diabetes has been increasing at alarming rate over the past three decades. This metabolic disorder, characterized by chronic hyperglycemia, leads to further severe damages like abnormally great thrust, excessive appetite, overweigh, blindness, excessive urination, cardiovascular complications, as well as renal and neurodegenerative diseases 1-6. There are three main diabetes types among which type 2 or non-insulin dependent (T2DM) is the most common one, mainly treated by controlling the digestive enzyme activities such as α-glucosidase 7-9. α-Glucosidase, found in the brush-border surface membrane of intestinal cells, plays catalyzing role in the carbohydrate digestion process by which the postprandial blood glucose levels increases. Preventing the glucose release in the bloodstream, the α-glucosidase inhibitors control T2DM 10. Additionally, this enzyme has a pivotal role in the biosynthesis of glycoprotein, therefore, its inhibitors have possessed anticancer, antitumor, antiviral, and immunoregulatory properties 11-15. Acrabose, miglitol, voglibose, and deoxynojirimycin have clinically been used to restrict the α-glucosidase activity 16. Considering the side effects and absorption problems associated with these drugs, new scaffolds should be synthesized and evaluated by medicinal chemists to extend the library of compounds 17-25. Pyrazoles are common structural motif in numerous drugs 26 and biologically active compounds showing activities such as anti-cancer 27,28 , anti-inflammatory 29 , anti-hypertensive 30 , cannabinoid receptor antagonist 31 , dopaminergic receptor antagonist 32 , and α-glucosidase inhibitors 33. Pyrazoles have been used to synthesize

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Section: Methodsmentioning

confidence: 99%

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Peytam

Adib

Shourgeshty

et al. 2020

Sci Rep

Self Cite

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“…Quinoline is a versatile heterocyclic moiety having diverse spectrum of biological activities including anti-Alzheimer's [12], anticancer [13], anticonvulsant [14], antidiabetic [15], antihypertensive [16], anti-inflammatory [17], antimicrobial [18] and ubiquitination inhibition [19] activities. In this review we hereby report anti-MRSA activity of quinoline derivatives reported so far.…”

Section: Quinoline Derivatives As Anti-mrsa Agentsmentioning

confidence: 99%

A review on quinoline derivatives as anti-methicillin resistant Staphylococcus aureus (MRSA) agents

Kumar

2020

BMC Chemistry

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Methicillin Resistant Staphylococcus aureus (MRSA) consists of strains of S. aureus which are resistant to methicillin. The resistance is due to the acquisition of mecA gene which encodes PBP2a unlike of any PBPs normally produced by S. aureus. PBP2a shows unusually low β-Lactam affinity and remains active to allow cell wall synthesis at normally lethal β-Lactam concentrations. MRSA can cause different types of infections like Healthcare associated MRSA, Community associated MRSA and Livestock associated MRSA infections. It causes skin lesions, osteomyelitis, endocarditis and furunculosis.To treat MRSA infections, only a few options are available like vancomycin, clindamycin, co-trimoxazole, fluoroquinolones or minocycline and there is a dire need of discovering new antibacterial agents that can effectively treat MRSA infections. In the current review, an attempt has been made to compile the data of quinoline derivatives possessing anti-MRSA potential reported to date.

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“…Wide spectrums of biological activities of quinoline compounds have been reviewed by many authors . Quinoline containing compounds display a wide range of biological activities including insecticidal, antimicrobial, antimalarial, anti‐amoebic, analgesic, vasorelaxing, antidiabetic, antimicobcterial, anticancer, anti‐inflammatory, antihypertensive, antiulcer and anti‐HIV activities. Some clinically used drug molecules based on quinoline heterocycle are presented (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Quinoline‐1,3‐Oxazole Hybrids: Syntheses, Anticancer Activity and Molecular Docking Studies

2020

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In continuation of the synthesis of potent quinoline based anticancer agents, a series of novel quinoline-1,3-oxazole hybrids 15 a-l were synthesized by the condensation reaction of 2-aryl-5-methyl-1,3-oxazole-4-carbaldehydes 10 a-f and 6bromo/6-chloro-2-methyl-quinolin-4-yl-hydrazines 14 a/b in good yield. Out of twelve, ten of the synthesized compounds were selected by the National Cancer Institute, USA for anticancer activity screening against 60 different human cancer cell lines representing nine types of cancer. Nine compounds were displayed outstanding antiproliferative activity with GI 50 values ranging from 0.26 to 25.6 μM and LC 50 values ranging from 2.96 μM to > 100 μM. The mean MG-MID values of GI 50 , TGI, and LC 50 were compared with the methotrexate and four compounds 15 b, 15 d, 15 e, 15 f emerged with important GI 50 < 2.0 μM. Among all compounds screened, 15 d displayed the highest potency as a cytotoxic molecule. Moreover, new hybrids were also studied for molecular docking into the active binding site of DNA topoisomerase I (htopoI) to understand the binding mode and favorable interactions of active compounds into binding sites of topoisomerase enzyme.[a] Prof.

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Design, synthesis and in vitro α-glucosidase inhibition of novel dihydropyrano[3,2-c]quinoline derivatives as potential anti-diabetic agents

Cited by 80 publications

References 21 publications

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

A review on quinoline derivatives as anti-methicillin resistant Staphylococcus aureus (MRSA) agents

Quinoline‐1,3‐Oxazole Hybrids: Syntheses, Anticancer Activity and Molecular Docking Studies

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