Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in t...
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doaj-251ca1e7db0c4945a61c81d54db4b4272020-11-24T22:36:30ZengMDPI AGMolecules1420-30492015-10-012010184371846310.3390/molecules201018437molecules201018437Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine NucleosidesSakilam Satishkumar0Prasanna K. Vuram1Siva Subrahmanyam Relangi2Venkateshwarlu Gurram3Hong Zhou4Robert J. Kreitman5Michelle M. Martínez Montemayor6Lijia Yang7Muralidharan Kaliyaperumal8Somesh Sharma9Narender Pottabathini10Mahesh K. Lakshman11Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USADepartment of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USADiscovery and Analytical Services, GVK Biosciences Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076, IndiaDiscovery and Analytical Services, GVK Biosciences Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076, IndiaClinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USAClinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USADepartment of Biochemistry, Universidad Central del Caribe-School of Medicine, P. O. Box 60327, Bayamón, PR 00960, USADepartment of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USADiscovery and Analytical Services, GVK Biosciences Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076, IndiaDiscovery and Analytical Services, GVK Biosciences Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076, IndiaDiscovery and Analytical Services, GVK Biosciences Pvt. Ltd., 28A IDA Nacharam, Hyderabad 500076, IndiaDepartment of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, NY 10031, USACladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active.http://www.mdpi.com/1420-3049/20/10/18437cladribinenucleosideguanosinebenzotriazole(benzotriazol-1yl-oxy)-tris(dimethylamino)phosphonium hexafluorophosphateBOP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sakilam Satishkumar Prasanna K. Vuram Siva Subrahmanyam Relangi Venkateshwarlu Gurram Hong Zhou Robert J. Kreitman Michelle M. Martínez Montemayor Lijia Yang Muralidharan Kaliyaperumal Somesh Sharma Narender Pottabathini Mahesh K. Lakshman |
spellingShingle |
Sakilam Satishkumar Prasanna K. Vuram Siva Subrahmanyam Relangi Venkateshwarlu Gurram Hong Zhou Robert J. Kreitman Michelle M. Martínez Montemayor Lijia Yang Muralidharan Kaliyaperumal Somesh Sharma Narender Pottabathini Mahesh K. Lakshman Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides Molecules cladribine nucleoside guanosine benzotriazole (benzotriazol-1yl-oxy)-tris(dimethylamino)phosphonium hexafluorophosphate BOP |
author_facet |
Sakilam Satishkumar Prasanna K. Vuram Siva Subrahmanyam Relangi Venkateshwarlu Gurram Hong Zhou Robert J. Kreitman Michelle M. Martínez Montemayor Lijia Yang Muralidharan Kaliyaperumal Somesh Sharma Narender Pottabathini Mahesh K. Lakshman |
author_sort |
Sakilam Satishkumar |
title |
Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides |
title_short |
Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides |
title_full |
Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides |
title_fullStr |
Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides |
title_full_unstemmed |
Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides |
title_sort |
cladribine analogues via o6-(benzotriazolyl) derivatives of guanine nucleosides |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2015-10-01 |
description |
Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active. |
topic |
cladribine nucleoside guanosine benzotriazole (benzotriazol-1yl-oxy)-tris(dimethylamino)phosphonium hexafluorophosphate BOP |
url |
http://www.mdpi.com/1420-3049/20/10/18437 |
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