Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783729002742022144 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8311656 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT otaibiahmedal biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT sherwanisubuhi biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT alzahranisalmaahmed biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT alshammarieidamohammed biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT khanwahidali biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT alsukaibiabdulmohsenkhalafd biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT khanshahpernazeer biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia AT khanmohdwajidali biologicallyactiveaaminoamideanalogsandgdtcellsauniqueanticancerapproachforleukemia |