Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents

Sidhom, Peter A.; El-Bastawissy, Eman; Salama, Abeer; El‐Moselhy, Tarek F.

doi:10.1016/j.bioorg.2021.105054

Cited by 14 publications

(14 citation statements)

References 57 publications

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“…The modified Clemens method was used to prepare the five acetoacetate derivatives ( 2a–f ) (Scheme ) (Supporting Information Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…25 Hantzsch synthesis and Meyer modification could be an epitomic model for MCRs. The modified Clemens method 26 was used to prepare the five acetoacetate derivatives (2a−f) (Scheme 1) 8 (Supporting Information Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…Compounds 2a−f and 4a−d were obtained as reported earlier by our research team. 8 4.1.1. Experimental Methodology for Synthesis of 4a−f.…”

Section: Methodsmentioning

confidence: 99%

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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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“…The modified Clemens method was used to prepare the five acetoacetate derivatives ( 2a–f ) (Scheme ) (Supporting Information Table S1).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2022

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“…Dihydropyridine derivatives have occupied a prominent place in medicinal chemistry because of their success as a central core in many drugs and are known for their multi‐receptor affinities with targeted enzymes [1–3] . The dihydropyridine group consists of numerous drugs with diverse pharmacokinetic profiles and biological practices and responses [4,5] .…”

Section: Introductionmentioning

confidence: 99%

“…Dihydropyridine derivatives have occupied a prominent place in medicinal chemistry because of their success as a central core in many drugs and are known for their multi-receptor affinities with targeted enzymes. [1][2][3] The dihydropyridine group consists of numerous drugs with diverse pharmacokinetic profiles and biological practices and responses. [4,5] They have attracted a lot of interest due to their significant biological applications such as antitumor, antihypertensive, anticonvulsant, cytotoxic, and significant analgesic activities.…”

Section: Introductionmentioning

confidence: 99%

Microwave‐Assisted Synthesis of 4‐Aryl‐1,4‐dihydropyridines as Potent Anticancer Agent and Their In‐Silico Studies

et al. 2022

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In our effort directed toward the discovery of novel potent anticancer agents, a large library of novel 4‐aryl‐1,4‐dihydropyridines (23‐58) with heterocyclic ring at 4, position of aryl group has been synthesized through Hantzsch synthesis. These synthesized hybrids have been well characterized and evaluated for their cytotoxic activities against a panel of human cancer cell lines viz. EAC, HEK, and MCF cell lines by MTT assay. The cytotoxic activity has been revealed by the effects of various types of substituent present on the dihydropyridine ring. All the synthetics (23‐58) have shown good potency against EAC cell line. However, compounds 36, 40, 42, and 54 have displayed significant inhibitory potential against both EAC and MCF‐7 cell lines. In addition, these promising analogues have been selected for their molecular docking studies against 5TVQ protein to know the binding affinity which was identified to be a plausible target site. Compound 42 has exerted the highest inhibition effect on cancerous cells and more potency than the reference drug, doxorubicin even at low concentration (1μg/ml) and showed non‐toxicity to human normal cells suggesting high safety to normal cells. Compound 42 has also shown the highest docking score and inhibition constant which could be regarded as convincing lead for further clinical pursuit.

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Synthesis, Biological Evaluation, in silico ADMET and Molecular Docking of new 1,4‐Dihydropyridine Derivatives Bearing Ether Substitution as Calcium Channel Blockers

Zare,

Hashemi,

Hassani

et al. 2023

ChemistrySelect

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A set of 1,4‐dihydropyridine derivatives were synthesized, possessing methyl or ethyl esters at positions 3 and 5, an aliphatic or aromatic ether group at position 2, and a thienyl ring at position 4. The calcium channel blocking activity of these derivatives was investigated using K+‐induced contraction on the longitudinal smooth muscles of guinea pig ileum (GPILSM). Our findings showed that the derivatives had IC50 ranging from 0.5 to 5.2 μM. Among the synthesized compounds, compound including methoxy group in position 2 and ethyl acetate in positions 3 and 5, with IC50=0.55±0.58 μM was almost comparable to that of nifedipine (IC50=0.27±1.23 μM). The results of docking studies and biological evaluation of synthetic compounds were consistent. According to the physicochemical and drug‐likeness parameters, it is predicted that the synthesized compounds can be a suitable candidate for calcium channel blocking.

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Revisiting ageless antiques; synthesis, biological evaluation, docking simulation and mechanistic insights of 1,4-Dihydropyridines as anticancer agents

Cited by 14 publications

References 57 publications

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

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

Microwave‐Assisted Synthesis of 4‐Aryl‐1,4‐dihydropyridines as Potent Anticancer Agent and Their In‐Silico Studies

Synthesis, Biological Evaluation, in silico ADMET and Molecular Docking of new 1,4‐Dihydropyridine Derivatives Bearing Ether Substitution as Calcium Channel Blockers

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