Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies
Background and purpose: Antiplatelet agents can diminish the chance of coronary heart diseases due to the prevention of unusual clotting in the arteries by inhibiting platelet aggregation and avoiding the formation of a blood clot. This mechanism can help to prevent ischemic stroke likewise. To impr...
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Wolters Kluwer Medknow Publications
2022
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oai:doaj.org-article:4ac94315828a4821975b569668718b3e2021-11-19T12:17:03ZNovel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies1735-53621735-941410.4103/1735-5362.329926https://doaj.org/article/4ac94315828a4821975b569668718b3e2022-01-01T00:00:00Zhttp://www.rpsjournal.net/article.asp?issn=1735-5362;year=2022;volume=17;issue=1;spage=53;epage=65;aulast=Tavilihttps://doaj.org/toc/1735-5362https://doaj.org/toc/1735-9414Background and purpose: Antiplatelet agents can diminish the chance of coronary heart diseases due to the prevention of unusual clotting in the arteries by inhibiting platelet aggregation and avoiding the formation of a blood clot. This mechanism can help to prevent ischemic stroke likewise. To improve the activity of these drugs and reduce their side effects, further studies are required. Experimental approach: Based on the previous studies representing the promising antiplatelet activity of indole hydrazones, a series of their homologs containing twenty-one compounds were prepared in two steps. First, alkylation reaction on the nitrogen of the indole ring, and second, chiff base formation by condensation of a primary amine and N-substituted indole-3 carbaldehyde. Consequently, their platelet anti-aggregation activity was evaluated based on the Born turbidimetric method. Findings/Results: Most of the compounds exhibited noticeable activity against platelet aggregation induced by arachidonic acid. Amongst them, two compounds 2e and 2f showed higher activity with IC50 values that made comparable to indomethacin and acetylsalicylic acid as standard drugs and had no toxicity on platelets. Conclusion and implications: The synthesized compounds exhibited promising activity against arachidonic acid-induced aggregation; however, none of them showed noticeable antiplatelet activity induced by adenosine di-phosphate. Chemical structure comparison of the prepared derivatives indicated the existence of a lipophilic medium-sized group on the phenyl ring increased their activity. In addition, the docking studies confirmed this hydrophobic interaction in the lipophilic pocket of cyclooxygenase-1 enzyme suggesting that hydrophobicity of this region plays a pivotal role in the anti-platelet activity of these compounds. To prove this finding, the enzymatic evaluation with the target enzyme is required.Navid TaviliShaya MokhtariHafezeh SalehabadiMarjan EsfahanizadehShohreh MohebbiWolters Kluwer Medknow Publicationsarticleantiplatelet aggregation; indole; synthesis; turbidimetric assay.Pharmacy and materia medicaRS1-441ENResearch in Pharmaceutical Sciences, Vol 17, Iss 1, Pp 53-65 (2022) |
| institution |
DOAJ |
| collection |
DOAJ |
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EN |
| topic |
antiplatelet aggregation; indole; synthesis; turbidimetric assay. Pharmacy and materia medica RS1-441 |
| spellingShingle |
antiplatelet aggregation; indole; synthesis; turbidimetric assay. Pharmacy and materia medica RS1-441 Navid Tavili Shaya Mokhtari Hafezeh Salehabadi Marjan Esfahanizadeh Shohreh Mohebbi Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| description |
Background and purpose: Antiplatelet agents can diminish the chance of coronary heart diseases due to the prevention of unusual clotting in the arteries by inhibiting platelet aggregation and avoiding the formation of a blood clot. This mechanism can help to prevent ischemic stroke likewise. To improve the activity of these drugs and reduce their side effects, further studies are required.
Experimental approach: Based on the previous studies representing the promising antiplatelet activity of indole hydrazones, a series of their homologs containing twenty-one compounds were prepared in two steps. First, alkylation reaction on the nitrogen of the indole ring, and second, chiff base formation by condensation of a primary amine and N-substituted indole-3 carbaldehyde. Consequently, their platelet anti-aggregation activity was evaluated based on the Born turbidimetric method.
Findings/Results: Most of the compounds exhibited noticeable activity against platelet aggregation induced by arachidonic acid. Amongst them, two compounds 2e and 2f showed higher activity with IC50 values that made comparable to indomethacin and acetylsalicylic acid as standard drugs and had no toxicity on platelets.
Conclusion and implications: The synthesized compounds exhibited promising activity against arachidonic acid-induced aggregation; however, none of them showed noticeable antiplatelet activity induced by adenosine di-phosphate. Chemical structure comparison of the prepared derivatives indicated the existence of a lipophilic medium-sized group on the phenyl ring increased their activity. In addition, the docking studies confirmed this hydrophobic interaction in the lipophilic pocket of cyclooxygenase-1 enzyme suggesting that hydrophobicity of this region plays a pivotal role in the anti-platelet activity of these compounds. To prove this finding, the enzymatic evaluation with the target enzyme is required. |
| format |
article |
| author |
Navid Tavili Shaya Mokhtari Hafezeh Salehabadi Marjan Esfahanizadeh Shohreh Mohebbi |
| author_facet |
Navid Tavili Shaya Mokhtari Hafezeh Salehabadi Marjan Esfahanizadeh Shohreh Mohebbi |
| author_sort |
Navid Tavili |
| title |
Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| title_short |
Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| title_full |
Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| title_fullStr |
Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| title_full_unstemmed |
Novel N-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| title_sort |
novel n-substituted indole hydrazones as potential antiplatelet agents: synthesis, biological evaluations, and molecular docking studies |
| publisher |
Wolters Kluwer Medknow Publications |
| publishDate |
2022 |
| url |
https://doaj.org/article/4ac94315828a4821975b569668718b3e |
| work_keys_str_mv |
AT navidtavili novelnsubstitutedindolehydrazonesaspotentialantiplateletagentssynthesisbiologicalevaluationsandmoleculardockingstudies AT shayamokhtari novelnsubstitutedindolehydrazonesaspotentialantiplateletagentssynthesisbiologicalevaluationsandmoleculardockingstudies AT hafezehsalehabadi novelnsubstitutedindolehydrazonesaspotentialantiplateletagentssynthesisbiologicalevaluationsandmoleculardockingstudies AT marjanesfahanizadeh novelnsubstitutedindolehydrazonesaspotentialantiplateletagentssynthesisbiologicalevaluationsandmoleculardockingstudies AT shohrehmohebbi novelnsubstitutedindolehydrazonesaspotentialantiplateletagentssynthesisbiologicalevaluationsandmoleculardockingstudies |
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