RT Journal Article
T1 n-Tuples on Scaffold Diversity Inspired by Drug Hybridisation to Enhance Drugability: Application to Cytarabine
A1 García-Castro, Miguel
A1 Fuentes-Ríos, David
A1 López-Romero, Juan Manuel
A1 Romero, Antonio
A1 Moya-Utrera, Federico
A1 Díaz-Morilla, Amelia
A1 Sarabia-García, Francisco Ramón
K1 Química farmacéutica
AB A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of different commercial drugs with cytarabine, a synthetic arabinonucleoside derived from two marine natural products, spongouridine and spongothymidine. The new methodology explores the virtual chemical-factorial combination of different commercial drugs (immunosuppressant, antibiotic, antiemetic, anti-inflammatory, and anticancer) with the anticancer drug cytarabine. Real chemical combinations were designed and synthesised for 8-duples, obtaining a small representative library of interesting organic molecules to be biologically tested as proof of concept. The synthesised library contains classical molecular properties regarding the Lipinski rules and/or beyond rules of five (bRo5) and is represented by the covalent combination of the anticancer drug cytarabine with ibuprofen, flurbiprofen, folic acid, sulfasalazine, ciprofloxacin, bortezomib, and methotrexate. The insertion of specific nomenclature could be implemented into artificial intelligence algorithms in order to enhance the efficiency of drug-hunting programs. The novel methodology has proven useful for the straightforward synthesis of most of the theoretically proposed duples and, in principle, could be extended to any other central drug.
PB MDPI
YR 2023
FD 2023-12-13
LK https://hdl.handle.net/10630/29402
UL https://hdl.handle.net/10630/29402
LA eng
NO García-Castro, M.; Fuentes-Rios, D.; López-Romero, J.M.; Romero, A.; Moya-Utrera, F.; Díaz-Morilla, A.; Sarabia, F. n-Tuples on Scaffold Diversity Inspired by Drug Hybridisation to Enhance Drugability: Application to Cytarabine. Mar. Drugs 2023, 21, 637. https://doi.org/10.3390/md21120637
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026