Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors

Almatary, Aya M.; Elmorsy, Mohammad A.; Husseiny, Walaa M. El; Selim, Khalid B.; El‐Sayed, Magda A.‐A.

doi:10.1002/ardp.201700403

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…The search for newer activities for this class of compounds is intensifying as a growing number of activities are reported [ 13 , 14 ]. Additionally, substitutions such as O-, N- and S- were found to play an important role in the modification of both the pharmacokinetic and pharmacodynamic properties of the heterocyclic compounds [ 15 ]. Hence, the present study was planned to screen the new synthesized derivatives of thiazole acetic acid for cardiovascular effects using isolated hearts and aortas in experimental rats.…”

Section: Introductionmentioning

confidence: 99%

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels

Raghunatha

Inamdar

Asdaq³

et al. 2022

Molecules

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Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.

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Section: Introductionmentioning

confidence: 99%

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels

Raghunatha

Inamdar

Asdaq³

et al. 2022

Molecules

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Novel diaryl ether derivatives as InhA inhibitors: Design, synthesis and antimycobacterial activity

Abdelaziz

Othman

Abdel‐Aziz

et al. 2022

Bioorganic Chemistry

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Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition

El-Husseiny

El‐Sayed

El‐Azab

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of 24 compounds was synthesised based on a 2-cyclopentyloxyanisole scaffold 3-14 and their in vitro antitumor activity was evaluated. Compounds 4a, 4b, 6b, 7b, 13, and 14 had the most potent antitumor activity (IC 50 range: 5.13-17.95 lM), compared to those of the reference drugs celecoxib, afatinib, and doxorubicin. The most active derivatives 4a, 4b, 7b, and 13 were evaluated for their inhibitory activity against COX-2, PDE4B, and TNF-a. Compounds 4a and 13 potently inhibited TNF-a (IC 50 values: 2.01 and 6.72 lM, respectively) compared with celecoxib (IC 50 ¼6.44 lM). Compounds 4b and 13 potently inhibited COX-2 (IC 50 values: 1.08 and 1.88 lM, respectively) comparable to that of celecoxib (IC 50 ¼0.68 lM). Compounds 4a, 7b, and 13 inhibited PDE4B (IC 50 values: 5.62, 5.65, and 3.98 lM, respectively) compared with the reference drug roflumilast (IC 50 ¼1.55 lM). The molecular docking of compounds 4b and 13 with the COX-2 and PDE4B binding pockets was studied. HIGHLIGHTS Antitumor activity of new synthesized cyclopentyloxyanisole scaffold was evaluated. The powerful antitumor 4a, 4b, 6b, 7b & 13 were assessed as COX-2, PDE4B & TNF-a inhibitors. Compounds 4a, 7b, and 13 exhibited COX-2, PDE4B, and TNF-a inhibition. Compounds 4b and 13 showed strong interactions at the COX-2 and PDE4B binding pockets.

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Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors

Cited by 3 publications

References 45 publications

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels

New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels

Novel diaryl ether derivatives as InhA inhibitors: Design, synthesis and antimycobacterial activity

Synthesis, antitumor activity, and molecular docking study of 2-cyclopentyloxyanisole derivatives: mechanistic study of enzyme inhibition

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