dc.contributor.author |
Alagoz, MA |
|
dc.contributor.author |
Oh, JM |
|
dc.contributor.author |
Zenni, YN |
|
dc.contributor.author |
Ozdemir, Z |
|
dc.contributor.author |
Abdelgawad, MA |
|
dc.contributor.author |
Naguib, IA |
|
dc.contributor.author |
Ghoneim, MM |
|
dc.contributor.author |
Gambacorta, N |
|
dc.contributor.author |
Nicolotti, O |
|
dc.contributor.author |
Kim, H |
|
dc.contributor.author |
Mathew, B |
|
dc.date.accessioned |
2022-10-05T13:00:56Z |
|
dc.date.available |
2022-10-05T13:00:56Z |
|
dc.date.issued |
2022 |
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dc.identifier.uri |
http://hdl.handle.net/11616/62207 |
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dc.description.abstract |
Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 mu M, followed by TR2 (IC50 = 0.27 mu M). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with K-i values of 0.230 +/- 0.004 and 0.149 +/- 0.016 mu M, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases. |
|
dc.description.abstract |
C1 [Alagoz, Mehmet Abdullah; Zenni, Yaren Nur; Ozdemir, Zeynep] Inonu Univ, Fac Pharm, Dept Pharmaceut Chem, TR-44280 Malatya, Turkey. |
|
dc.description.abstract |
[Oh, Jong Min; Kim, Hoon] Sunchon Natl Univ, Dept Pharm, Sunchon 57922, South Korea. |
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dc.description.abstract |
[Oh, Jong Min; Kim, Hoon] Sunchon Natl Univ, Res Inst Life Pharmaceut Sci, Sunchon 57922, South Korea. |
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dc.description.abstract |
[Abdelgawad, Mohamed A.] Jouf Univ, Coll Pharm, Dept Pharmaceut Chem, Sakaka 72341, Al Jouf, Saudi Arabia. |
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dc.description.abstract |
[Naguib, Ibrahim A.] Taif Univ, Coll Pharm, Dept Pharmaceut Chem, POB 11099, Taif 21944, Saudi Arabia. |
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dc.description.abstract |
[Ghoneim, Mohammed M.] AlMaarefa Univ, Fac Pharm, Dept Pharm Practice, Ad Diriyah 13713, Saudi Arabia. |
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dc.description.abstract |
[Gambacorta, Nicola; Nicolotti, Orazio] Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Via E Orabona 4, I-70125 Bari, Italy. |
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dc.description.abstract |
[Mathew, Bijo] Amrita Vishwa Vidyapeetham, Dept Pharmaceut Chem, Amrita Sch Pharm, AIMS Hlth Sci Campus, Kochi 682041, Kerala, India. |
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dc.source |
MOLECULES |
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dc.title |
Development of a Novel Class of Pyridazinone Derivatives as Selective |
|