Synthesis, anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors

Praveenkumar, E.; Gurrapu, Nirmala; Kolluri, Prashanth Kumar; Yerragunta, Vishwanadham; Kunduru, Bharathi Reddy; Subhashini, N

doi:10.1016/j.bioorg.2019.103056

Cited by 19 publications

(9 citation statements)

References 28 publications

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“…Overall, compounds 80 (−9.758) and 81 (−8.595) demonstrated highly stable binding patterns for 11β-HSD1 in molecular docking studies. 217 Larijani et al reported excellent α-glucosidase activity for coumarin-fused pyridines (Figure 41). Most of their compounds had IC 50 values in the range of 101.0±2.0 to 227.3±1.4 μM, whereas the standard drug acarbose had an IC 50 value of 750.0±1.5 μM.…”

Section: Anti-inflammatory Drugs and Active Compoundsmentioning

confidence: 99%

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

Ling

Hao

Liang

et al. 2021

DDDT

193

114

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Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

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Section: Anti-inflammatory Drugs and Active Compoundsmentioning

confidence: 99%

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design

Ling

Hao

Liang

et al. 2021

DDDT

193

114

View full text Add to dashboard Cite

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“…The final piece of the mechanistic puzzle was discovering how DHPs lowered the blood glucose level in an insulin-independent pattern. To realize this unknown mechanism(s), four targets were proposed based on data collected from previous reports , along with our suggestions. These targets were dipeptidyl peptidase-4 (DPP-4), α-glucosidase, α-amylase, and the sodium/glucose cotransporter-2 (SGLT2) (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…The 1,4-dihydropyridine (DHP) nucleus has proved to be a biologically advantaged and versatile platform, displaying various biotic actions, such as anticancer, − anticonvulsant, − antidiabetic, − anti-inflammatory, , and antihypertensive, for the treatment of vasospastic angina, as antibacterial agents and antifungal agents, as well as in the management of tuberculosis …”

Section: Introductionmentioning

confidence: 99%

Mechanistic Insight of Synthesized 1,4-Dihydropyridines as an Antidiabetic Sword against Reactive Oxygen Species

et al. 2022

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The pharmacologically privileged DHP derivatives were synthesized using the pragmatic multicomponent Hantzsch synthesis to screen the antidiabetic activity. Initially, the candidates were screened using an in vivo blood glucose test, where compound 8b showed the most prominent antidiabetic effect (% potency = 218%) compared to glimepiride. Then, a propositioned structure–activity relationship study was executed to reveal that longer side chains decreased the DHP’s antidiabetic action. Mechanistically, compound 8b diminished ROS in β-cells and muscle cells simultaneously, which was proved by enhanced serum biochemical markers. Also, compound 8b decreased blood glucose by α-glucosidase inhibition (IC50 = 4.48 ± 0.32 μM), compared to acarbose (7.40 ± 0.41 μM), based selectively on the plasma window of 8b. Acarbose demonstrated auspicious inhibitor activity according to the binding affinity (ΔG binding), which was slightly lower than that of compound 8b (−54.7 and −46.8 kcal/mol, respectively). During the 100 ns molecular dynamics simulations, the structural and energetic assessments exposed the high consistency of compound 8b to bind to the α-glucosidase.

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“…Molecular docking studies revealed that compound 75 showed a stable binding pattern (−9.758) with human 11-β-HSD1 ( Scheme 76 ). 106 …”

Section: Synthetic Advancesmentioning

confidence: 99%