11a-N-tosyl-5-carbapterocarpans: Synthesis, antineoplastic evaluation and in silico prediction of ADMETox properties.
Bioorg Chem
; 80: 585-590, 2018 10.
Article
in En
| MEDLINE
| ID: mdl-30036814
11a-N-tosyl-5-carbapterocarpans (5a-c and 6a-c), 9-N-tosyl-4,4a,9,9a-tetrahydro-3H-carbazole (7), 11a-N-tosyl-5-carbapterocarpen (8) analogues of LQB-223 (4a), were synthesized through palladium catalyzed azaarylation of substituted dihydronaphtalenes (14a-c) and cyclohexadiene (15), respectively, with N-tosyl-o-iodoaniline (11). In order to understand the role of the N-tosyl moiety for the pharmacological activity, the azacarbapterocarpen (9) was also synthesized by Fischer indol reaction. The structural requirements at the A and D-rings for the antineoplastic activity toward human leukemias and breast cancer cells were evaluated as well. Substitutions on the A-ring of 4a and analogues alter the effect on different breast cancer subtypes. On the other hand, A-ring is not essential for antileukemic activity since compound 7, which does not contain the A-ring, showed efficacy with high selectivity indices for drug-resistant leukemias. On the other hand, substitutions on the D-ring of 4a for fluorine or iodine did not improve the antileukemic activity. In silico studies concerning Lipinskís rule of five, ADMET properties and drug scores of those compounds were performed, indicating good physicochemical properties for all compounds, in special for compound 7.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tosyl Compounds
/
Pterocarpans
/
Antineoplastic Agents
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2018
Document type:
Article
Affiliation country:
Brazil
Country of publication:
United States