3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

Adel S. Girgis; Siva S. Panda; Aladdin M. Srour; Anwar Abdelnaser; Soad Nasr; Yassmin Moatasim; Omnia Kutkat; Ahmed El Taweel; Ahmed Kandeil; Ahmed Mostafa; Mohamed A. Ali; Nehmedo G. Fawzy; Mohamed S. Bekheit; El Sayed M. Shalaby; Lara Gigli; Walid Fayad; Ahmed A.F. Soliman

doi:10.1016/j.bioorg.2021.105131

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

Adel S. Girgis, Siva S. Panda, Aladdin M. Srour, Anwar Abdelnaser, Soad Nasr, Yassmin Moatasim, Omnia Kutkat, Ahmed El Taweel, Ahmed Kandeil, Ahmed Mostafa, Mohamed A. Ali, Nehmedo G. Fawzy, Mohamed S. Bekheit, El Sayed M. Shalaby, Lara Gigli, Walid Fayad, Ahmed A.F. Soliman

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC₅₀ close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.

Original language	English (US)
Article number	105131
Journal	Bioorganic Chemistry
Volume	114
DOIs	https://doi.org/10.1016/j.bioorg.2021.105131
State	Published - Sep 2021

Keywords

Antitumor
Benzimidazole
Docking
Indole
SARS-CoV-2
VEGFR-2
c-Kit

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bioorg.2021.105131

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Girgis, A. S., Panda, S. S., Srour, A. M., Abdelnaser, A., Nasr, S., Moatasim, Y., Kutkat, O., El Taweel, A., Kandeil, A., Mostafa, A., Ali, M. A., Fawzy, N. G., Bekheit, M. S., Shalaby, E. S. M., Gigli, L., Fayad, W., & Soliman, A. A. F. (2021). 3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2. Bioorganic Chemistry, 114, Article 105131. https://doi.org/10.1016/j.bioorg.2021.105131

Girgis, AS, Panda, SS, Srour, AM, Abdelnaser, A, Nasr, S, Moatasim, Y, Kutkat, O, El Taweel, A, Kandeil, A, Mostafa, A, Ali, MA, Fawzy, NG, Bekheit, MS, Shalaby, ESM, Gigli, L, Fayad, W & Soliman, AAF 2021, '3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2', Bioorganic Chemistry, vol. 114, 105131. https://doi.org/10.1016/j.bioorg.2021.105131

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title = "3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2",

abstract = "Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC50 close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.",

keywords = "Antitumor, Benzimidazole, Docking, Indole, SARS-CoV-2, VEGFR-2, c-Kit",

author = "Girgis, {Adel S.} and Panda, {Siva S.} and Srour, {Aladdin M.} and Anwar Abdelnaser and Soad Nasr and Yassmin Moatasim and Omnia Kutkat and {El Taweel}, Ahmed and Ahmed Kandeil and Ahmed Mostafa and Ali, {Mohamed A.} and Fawzy, {Nehmedo G.} and Bekheit, {Mohamed S.} and Shalaby, {El Sayed M.} and Lara Gigli and Walid Fayad and Soliman, {Ahmed A.F.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = sep,

doi = "10.1016/j.bioorg.2021.105131",

language = "English (US)",

volume = "114",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

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TY - JOUR

T1 - 3-Alkenyl-2-oxindoles

T2 - Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

AU - Girgis, Adel S.

AU - Panda, Siva S.

AU - Srour, Aladdin M.

AU - Abdelnaser, Anwar

AU - Nasr, Soad

AU - Moatasim, Yassmin

AU - Kutkat, Omnia

AU - El Taweel, Ahmed

AU - Kandeil, Ahmed

AU - Mostafa, Ahmed

AU - Ali, Mohamed A.

AU - Fawzy, Nehmedo G.

AU - Bekheit, Mohamed S.

AU - Shalaby, El Sayed M.

AU - Gigli, Lara

AU - Fayad, Walid

AU - Soliman, Ahmed A.F.

PY - 2021/9

Y1 - 2021/9

N2 - Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC50 close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.

AB - Sets of 3-alkenyl-2-oxindoles (6,10,13) were synthesized in a facile synthetic pathway through acid dehydration (EtOH/HCl) of the corresponding 3-hydroxy-2-oxoindolines (5,9,12). Single crystal (10a,c) and powder (12a,26f) X-ray studies supported the structures. Compounds 6c and 10b are the most effective agents synthesized (about 3.4, 3.3 folds, respectively) against PaCa2 (pancreatic) cancer cell line relative to the standard reference used (Sunitinib). Additionally, compound 10b reveals antiproliferative properties against MCF7 (breast) cancer cell with IC50 close to that of Sunitinib. CAM testing reveals that compounds 6 and 10 demonstrated qualitative and quantitative decreases in blood vessel count and diameter with efficacy comparable to that of Sunitinib, supporting their anti-angiogenic properties. Kinase inhibitory properties support their multi-targeted inhibitory activities against VEGFR-2 and c-kit in similar behavior to that of Sunitinib. Cell cycle analysis studies utilizing MCF7 exhibit that compound 6b arrests the cell cycle at G1/S phase while, 10b reveals accumulation of the tested cell at S phase. Compounds 6a and 10b reveal potent antiviral properties against SARS-CoV-2 with high selectivity index relative to the standards (hydroxychloroquine, chloroquine). Safe profile of the potent synthesized agents, against normal cells (VERO-E6, RPE1), support the possible development of better hits based on the attained observations.

KW - Antitumor

KW - Benzimidazole

KW - Docking

KW - Indole

KW - SARS-CoV-2

KW - VEGFR-2

KW - c-Kit

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DO - 10.1016/j.bioorg.2021.105131

M3 - Article

C2 - 34243074

AN - SCOPUS:85113910786

SN - 0045-2068

VL - 114

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

M1 - 105131

ER -

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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