Novel Ag(I)-based 1,2,4-oxadiazole complexes: Synthesis, X-ray crystal structure, and biological evaluation as anticancer candidates

Mohammed Salah  Ayoup; Rabia E. Alashhab; Saied M.  Soliman; Hamida  Abdel-Hamid; David Bradford Cordes; Aidan McKay; Doaa A.  Ghareeb; Aliaa  Masoud; Asmaa E.  Kassab; Mohamed N.  Abd Al Moaty

doi:10.1002/aoc.7804

Novel Ag(I)-based 1,2,4-oxadiazole complexes: Synthesis, X-ray crystal structure, and biological evaluation as anticancer candidates

Mohammed Salah Ayoup, Rabia E. Alashhab, Saied M. Soliman, Hamida Abdel-Hamid, David Bradford Cordes, Aidan McKay, Doaa A. Ghareeb, Aliaa Masoud, Asmaa E. Kassab, Mohamed N. Abd Al Moaty

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Abstract

The 3,5-diaryl-1,2,4-oxadiazole scaffolds 2 and 3 were synthesized and used as ligands to obtain three novel Ag(I) complexes 4-6. The structure of the Ag(I) complexes 4-6 has been confirmed by single crystal X-ray diffraction. Complex 4 has the dinuclear formula [Ag(2)(NO₃₎]₂. 5 and 6 are monomeric complexes having the formula [Ag(3)₂(NO₃)] and [Ag(3)₂]ClO₄, respectively. In vitro, trypsin, ALDH2, and iNOS inhibition activities were assessed for the free ligands and their Ag(I) complexes. Interestingly, Ag(I) complexes 4-6 revealed more prominent trypsin inhibitory activity than the ligands 2 and 3. The oxadiazole derivative 3 and its Ag(I) complex (6) showed significant ALDH2 inhibition (45% and 55%, respectively). Complex 6 (IC₅₀ = 35.61 µM) surpassed its 1,2,4-oxadiazole ligand 3 (IC₅₀ = 88 µM) and evidenced the most prominent ALDH2 inhibitory activity. The oxadiazole derivative 3 and its corresponding Ag(I) complexes 5 and 6 showed significant iNOS inhibition (77.77 %, 84.12%, and 84.15%, respectively). With IC₅₀ values of 18.13, 18.15 and 13.96 µM, respectively, complex 6 is the most potent against iNOS, surpassing the reference standard.

Original language	English
Article number	e7804
Number of pages	12
Journal	Applied Organometallic Chemistry
Early online date	13 Oct 2024
DOIs	https://doi.org/10.1002/aoc.7804
Publication status	E-pub ahead of print - 13 Oct 2024

Keywords

1,2,4-oxadiazole
Ag(I)
ALDH2
iNOS
trypsin
X-ray structure

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Ayoup_2024_AOC_Novel-AgI_AAM_CCBY
Copyright © 2024 the Authors. This work has been made available online in accordance with the University of St Andrews Open Access policy. This accepted manuscript is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The final published version of this work is available at https://doi.org/10.1002/aoc.7804
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CCDC 2347251 - 2347253: Experimental Crystal Structure Determination
Ayoup, M. S. (Creator), Alashhab, R. E. (Creator), Soliman, S. M. (Creator), Abdel‐Hamid, H. (Creator), Cordes, D. B. (Creator), McKay, A. P. (Creator), Ghareeb, D. A. (Creator), Masoud, A. (Creator), Kassab, A. E. (Creator) & Al Moaty, M. N. A. (Creator), Cambridge Crystallographic Data Centre, 2024
DOI: 10.5517/ccdc.csd.cc2jshsm, https://dx.doi.org/10.5517/ccdc.csd.cc2jshvp and one more link, https://dx.doi.org/10.5517/ccdc.csd.cc2jshtn (show fewer)
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Ayoup, M. S., Alashhab, R. E., Soliman, S. M., Abdel-Hamid, H., Cordes, D. B., McKay, A., Ghareeb, D. A., Masoud, A., Kassab, A. E., & Abd Al Moaty, M. N. (2024). Novel Ag(I)-based 1,2,4-oxadiazole complexes: Synthesis, X-ray crystal structure, and biological evaluation as anticancer candidates. Applied Organometallic Chemistry, Article e7804. Advance online publication. https://doi.org/10.1002/aoc.7804

@article{a93cce0b98c146fe8abcd29bbadea396,

title = "Novel Ag(I)-based 1,2,4-oxadiazole complexes: Synthesis, X-ray crystal structure, and biological evaluation as anticancer candidates",

abstract = "The 3,5-diaryl-1,2,4-oxadiazole scaffolds 2 and 3 were synthesized and used as ligands to obtain three novel Ag(I) complexes 4-6. The structure of the Ag(I) complexes 4-6 has been confirmed by single crystal X-ray diffraction. Complex 4 has the dinuclear formula [Ag(2)(NO3)]2. 5 and 6 are monomeric complexes having the formula [Ag(3)2(NO3)] and [Ag(3)2]ClO4, respectively. In vitro, trypsin, ALDH2, and iNOS inhibition activities were assessed for the free ligands and their Ag(I) complexes. Interestingly, Ag(I) complexes 4-6 revealed more prominent trypsin inhibitory activity than the ligands 2 and 3. The oxadiazole derivative 3 and its Ag(I) complex (6) showed significant ALDH2 inhibition (45% and 55%, respectively). Complex 6 (IC50 = 35.61 µM) surpassed its 1,2,4-oxadiazole ligand 3 (IC50 = 88 µM) and evidenced the most prominent ALDH2 inhibitory activity. The oxadiazole derivative 3 and its corresponding Ag(I) complexes 5 and 6 showed significant iNOS inhibition (77.77 %, 84.12%, and 84.15%, respectively). With IC50 values of 18.13, 18.15 and 13.96 µM, respectively, complex 6 is the most potent against iNOS, surpassing the reference standard. ",

keywords = "1,2,4-oxadiazole, Ag(I), ALDH2, iNOS, trypsin, X-ray structure",

author = "Ayoup, {Mohammed Salah} and Alashhab, {Rabia E.} and Soliman, {Saied M.} and Hamida Abdel-Hamid and Cordes, {David Bradford} and Aidan McKay and Ghareeb, {Doaa A.} and Aliaa Masoud and Kassab, {Asmaa E.} and {Abd Al Moaty}, {Mohamed N.}",

note = "Funding: This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Project No. KFU241542).",

year = "2024",

month = oct,

day = "13",

doi = "10.1002/aoc.7804",

language = "English",

journal = "Applied Organometallic Chemistry",

issn = "0268-2605",

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T1 - Novel Ag(I)-based 1,2,4-oxadiazole complexes: Synthesis, X-ray crystal structure, and biological evaluation as anticancer candidates

AU - Ayoup, Mohammed Salah

AU - Alashhab, Rabia E.

AU - Soliman, Saied M.

AU - Abdel-Hamid, Hamida

AU - Cordes, David Bradford

AU - McKay, Aidan

AU - Ghareeb, Doaa A.

AU - Masoud, Aliaa

AU - Kassab, Asmaa E.

AU - Abd Al Moaty, Mohamed N.

N1 - Funding: This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Project No. KFU241542).

PY - 2024/10/13

Y1 - 2024/10/13

N2 - The 3,5-diaryl-1,2,4-oxadiazole scaffolds 2 and 3 were synthesized and used as ligands to obtain three novel Ag(I) complexes 4-6. The structure of the Ag(I) complexes 4-6 has been confirmed by single crystal X-ray diffraction. Complex 4 has the dinuclear formula [Ag(2)(NO3)]2. 5 and 6 are monomeric complexes having the formula [Ag(3)2(NO3)] and [Ag(3)2]ClO4, respectively. In vitro, trypsin, ALDH2, and iNOS inhibition activities were assessed for the free ligands and their Ag(I) complexes. Interestingly, Ag(I) complexes 4-6 revealed more prominent trypsin inhibitory activity than the ligands 2 and 3. The oxadiazole derivative 3 and its Ag(I) complex (6) showed significant ALDH2 inhibition (45% and 55%, respectively). Complex 6 (IC50 = 35.61 µM) surpassed its 1,2,4-oxadiazole ligand 3 (IC50 = 88 µM) and evidenced the most prominent ALDH2 inhibitory activity. The oxadiazole derivative 3 and its corresponding Ag(I) complexes 5 and 6 showed significant iNOS inhibition (77.77 %, 84.12%, and 84.15%, respectively). With IC50 values of 18.13, 18.15 and 13.96 µM, respectively, complex 6 is the most potent against iNOS, surpassing the reference standard.

AB - The 3,5-diaryl-1,2,4-oxadiazole scaffolds 2 and 3 were synthesized and used as ligands to obtain three novel Ag(I) complexes 4-6. The structure of the Ag(I) complexes 4-6 has been confirmed by single crystal X-ray diffraction. Complex 4 has the dinuclear formula [Ag(2)(NO3)]2. 5 and 6 are monomeric complexes having the formula [Ag(3)2(NO3)] and [Ag(3)2]ClO4, respectively. In vitro, trypsin, ALDH2, and iNOS inhibition activities were assessed for the free ligands and their Ag(I) complexes. Interestingly, Ag(I) complexes 4-6 revealed more prominent trypsin inhibitory activity than the ligands 2 and 3. The oxadiazole derivative 3 and its Ag(I) complex (6) showed significant ALDH2 inhibition (45% and 55%, respectively). Complex 6 (IC50 = 35.61 µM) surpassed its 1,2,4-oxadiazole ligand 3 (IC50 = 88 µM) and evidenced the most prominent ALDH2 inhibitory activity. The oxadiazole derivative 3 and its corresponding Ag(I) complexes 5 and 6 showed significant iNOS inhibition (77.77 %, 84.12%, and 84.15%, respectively). With IC50 values of 18.13, 18.15 and 13.96 µM, respectively, complex 6 is the most potent against iNOS, surpassing the reference standard.

KW - 1,2,4-oxadiazole

KW - Ag(I)

KW - ALDH2

KW - iNOS

KW - trypsin

KW - X-ray structure

U2 - 10.1002/aoc.7804

DO - 10.1002/aoc.7804

M3 - Article

SN - 0268-2605

JO - Applied Organometallic Chemistry

JF - Applied Organometallic Chemistry

M1 - e7804

ER -

Novel Ag(I)-based 1,2,4-oxadiazole complexes: Synthesis, X-ray crystal structure, and biological evaluation as anticancer candidates

Abstract

Keywords

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CCDC 2347251 - 2347253: Experimental Crystal Structure Determination

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