An Advanced Computational Evaluation for the Most Biologically Active Enantiomers of Chiral Anti-Cancer Agents.


Journal

Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649

Informations de publication

Date de publication:
2021
Historique:
received: 24 05 2020
revised: 06 10 2020
accepted: 26 10 2020
pubmed: 5 1 2021
medline: 18 1 2022
entrez: 4 1 2021
Statut: ppublish

Résumé

Cancer is a very dangerous disease whose treatment can be improved by removing the factors that cause side effects if the drugs prescribed for cancer are chiral in nature. A computational evaluation for the most biologically active enantiomeric form of chiral drugs attacking the DNA of the cell, was made for the first time, and compared with the experimental work done by others previously. All the enantiomeric structures of the drugs taken in the present study were obtained using Marvin sketch, and the structure of DNA to be docked with enantiomers, was obtained from the protein data bank. After that, all the enantiomers of the chiral drugs were docked with DNA one by one for the evaluation of the most biologically active enantiomeric form. The docking study showed that the different enantiomers interacted with DNA differently because of having different arrangements of atoms/groups. The binding affinity of one of the two enantiomeric forms was higher than that of another. R-methotrexate for breast cancer; R-mitotane for adrenocortical cancer; R-duvelisib for blood cancer, and S-irinotecan for colon cancer would be a suitable drug with less toxicity as well as other side effects.

Sections du résumé

BACKGROUND
Cancer is a very dangerous disease whose treatment can be improved by removing the factors that cause side effects if the drugs prescribed for cancer are chiral in nature.
OBJECTIVES
A computational evaluation for the most biologically active enantiomeric form of chiral drugs attacking the DNA of the cell, was made for the first time, and compared with the experimental work done by others previously.
METHODS
All the enantiomeric structures of the drugs taken in the present study were obtained using Marvin sketch, and the structure of DNA to be docked with enantiomers, was obtained from the protein data bank. After that, all the enantiomers of the chiral drugs were docked with DNA one by one for the evaluation of the most biologically active enantiomeric form.
RESULTS
The docking study showed that the different enantiomers interacted with DNA differently because of having different arrangements of atoms/groups. The binding affinity of one of the two enantiomeric forms was higher than that of another.
CONCLUSION
R-methotrexate for breast cancer; R-mitotane for adrenocortical cancer; R-duvelisib for blood cancer, and S-irinotecan for colon cancer would be a suitable drug with less toxicity as well as other side effects.

Identifiants

pubmed: 33390138
pii: ACAMC-EPUB-112863
doi: 10.2174/1871520621999201230233811
doi:

Substances chimiques

Antineoplastic Agents 0
Isoquinolines 0
Purines 0
duvelisib 610V23S0JI
Irinotecan 7673326042
Mitotane 78E4J5IB5J
DNA 9007-49-2
Methotrexate YL5FZ2Y5U1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2075-2081

Informations de copyright

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Auteurs

Mohd Suhail (M)

Department of Chemistry, Jamia Millia Islamia, (A Central University) Jamia Nagar, New Delhi-110025, India.

Imran Ali (I)

Department of Chemistry, Jamia Millia Islamia, (A Central University) Jamia Nagar, New Delhi-110025, India.

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Classifications MeSH