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Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia

Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to...

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Autores principales: Otaibi, Ahmed Al, Sherwani, Subuhi, Al-Zahrani, Salma Ahmed, Alshammari, Eida Mohammed, Khan, Wahid Ali, Alsukaibi, Abdulmohsen Khalaf D., Khan, Shahper Nazeer, Khan, Mohd Wajid Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311656/
https://www.ncbi.nlm.nih.gov/pubmed/34322393
http://dx.doi.org/10.3389/fonc.2021.706586
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author Otaibi, Ahmed Al
Sherwani, Subuhi
Al-Zahrani, Salma Ahmed
Alshammari, Eida Mohammed
Khan, Wahid Ali
Alsukaibi, Abdulmohsen Khalaf D.
Khan, Shahper Nazeer
Khan, Mohd Wajid Ali
author_facet Otaibi, Ahmed Al
Sherwani, Subuhi
Al-Zahrani, Salma Ahmed
Alshammari, Eida Mohammed
Khan, Wahid Ali
Alsukaibi, Abdulmohsen Khalaf D.
Khan, Shahper Nazeer
Khan, Mohd Wajid Ali
author_sort Otaibi, Ahmed Al
collection PubMed
description Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia. Biologically active α-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC(50) values of α-AAA-A and α-AAA-B against leukemia cancer cell lines (HL-60 and K562) were analyzed though MTT assay. Cytotoxic assay analyzed percent killing of leukemia cell lines due to the effect of γδ T cells alone or in combination with α-AAA-A or α-AAA-B. Synthesized biologically active molecule α-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with α-AAA-B (44% and 36% respectively). Similarly, α-AAA-A showed low IC(50) values for HL-60 (1.61 ± 0.11 μM) and K562 (3.01 ± 0.14 μM) compared to α-AAA-B (3.12 ± 0.15 μM and 6.21 ± 0.17 μM respectively). Additive effect of amide analogs and γδ T cells showed significantly high leukemia cancer cell killing as compared to γδ T cells alone. A unique combinational therapy with γδ T cells and biologically active anti-cancer molecules (α-AAA-A/B), concomitantly may be a promising cancer therapy.
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spelling pubmed-83116562021-07-27 Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia Otaibi, Ahmed Al Sherwani, Subuhi Al-Zahrani, Salma Ahmed Alshammari, Eida Mohammed Khan, Wahid Ali Alsukaibi, Abdulmohsen Khalaf D. Khan, Shahper Nazeer Khan, Mohd Wajid Ali Front Oncol Oncology Advanced stage cancers are aggressive and difficult to treat with mono-therapeutics, substantially decreasing patient survival rates. Hence, there is an urgent need to develop unique therapeutic approaches to treat cancer with superior potency and efficacy. This study investigates a new approach to develop a potent combinational therapy to treat advanced stage leukemia. Biologically active α-amino amide analogs (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylpropiolamide (α-AAA-A) and (RS)-N-(2-(cyclohexylamino)-2-oxo-1-phenylethyl)-N-phenylbut2-enamide (α-AAA-B) were synthesized using linear Ugi multicomponent reaction. Cytotoxicities and IC(50) values of α-AAA-A and α-AAA-B against leukemia cancer cell lines (HL-60 and K562) were analyzed though MTT assay. Cytotoxic assay analyzed percent killing of leukemia cell lines due to the effect of γδ T cells alone or in combination with α-AAA-A or α-AAA-B. Synthesized biologically active molecule α-AAA-A exhibited increased cytotoxicity of HL-60 (54%) and K562 (44%) compared with α-AAA-B (44% and 36% respectively). Similarly, α-AAA-A showed low IC(50) values for HL-60 (1.61 ± 0.11 μM) and K562 (3.01 ± 0.14 μM) compared to α-AAA-B (3.12 ± 0.15 μM and 6.21 ± 0.17 μM respectively). Additive effect of amide analogs and γδ T cells showed significantly high leukemia cancer cell killing as compared to γδ T cells alone. A unique combinational therapy with γδ T cells and biologically active anti-cancer molecules (α-AAA-A/B), concomitantly may be a promising cancer therapy. Frontiers Media S.A. 2021-07-12 /pmc/articles/PMC8311656/ /pubmed/34322393 http://dx.doi.org/10.3389/fonc.2021.706586 Text en Copyright © 2021 Otaibi, Sherwani, Al-Zahrani, Alshammari, Khan, Alsukaibi, Khan and Khan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Otaibi, Ahmed Al
Sherwani, Subuhi
Al-Zahrani, Salma Ahmed
Alshammari, Eida Mohammed
Khan, Wahid Ali
Alsukaibi, Abdulmohsen Khalaf D.
Khan, Shahper Nazeer
Khan, Mohd Wajid Ali
Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia
title Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia
title_full Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia
title_fullStr Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia
title_full_unstemmed Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia
title_short Biologically Active α-Amino Amide Analogs and γδ T Cells—A Unique Anticancer Approach for Leukemia
title_sort biologically active α-amino amide analogs and γδ t cells—a unique anticancer approach for leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311656/
https://www.ncbi.nlm.nih.gov/pubmed/34322393
http://dx.doi.org/10.3389/fonc.2021.706586
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