Finding alternatives to 5-fluorouracil: application of ensemble-based virtual screening for drug repositioning against human thymidylate synthase.
J Biomol Struct Dyn
; 41(11): 4873-4889, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-35538714
ABSTRACT
5-fluorouracil and analogs are used in the treatment of many solid tumours. However, there are many cases of resistance and high toxicity associated with 5-fluorouracil chemotherapy. Repurposing FDA drugs against human thymidylate synthase revealed a number of FDA drugs that have a potential to be further developed for the treatment of various cancers for which 5-fluorouracil and analogs have been used for chemotherapy. Four FDA drugs prioritized for further validation included Erismodegib, Irinotecan, Conivaptan and Ergotamine. The role of water in mediating drug interactions and its contribution to the total binding energy was also shown. MM-PBSA calculations revealed that the binding affinity was the lowest for the hTS-Ergotamine complex (-66.702 ± 1.807 kJ/mol) suggesting moderate inhibition despite a large energetic contribution from van der Waal interactions (-190.889 ± 1.027 kJ/mol).Communicated by Ramaswamy H. Sarma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fluorouracilo
/
Neoplasias
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2023
Tipo del documento:
Article
País de afiliación:
Tanzania