Synthesis of Indole-Linked Thiadiazoles and their Anticancer Action against Triple-Negative Breast Cancer.
Chem Biodivers
; 21(4): e202302000, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38427723
ABSTRACT
With a lack of targeted therapy and significantly high metastasis, heterogeneity, and relapse rates, Triple-Negative Breast Cancer (TNBC) offers substantial treatment challenges and demands more chemotherapeutic interventions. In the present study, indole-endowed thiadiazole derivatives have been synthesized and screened for antiproliferative potency against the triple-negative breast cancer MDA-MB-231â
cell line. Compound 4 h, possessing chlorophenyl moiety, displays the best anticancer potency (IC50 0.43â
µM) in the cell viability assay. The title compounds demonstrate substantial docking competency against the EGFR receptor (PDB ID 3POZ), validating their in-vitro ant proliferative action. With a high docking score (-9.9 to -8.7â
kcal/mol), the indole hybrids display significant binding propensity comparable to the co-crystallized ligand TAK-285 and occupy a similar strategic position in the active domain of the designated receptor. The quantum and electronic properties of the integrated templates are evaluated through DFT, and optimal values of the deduced global reactivity indices, such as energy gap, electronegativity, ionization potential, chemical potential, electrophilicity, etc., suggest their apt biochemical reactivity. The indole hybrids show near-appropriate pharmacokinetic efficacy and bioavailability in the in-silico studies, indicating their candidacy for potential drug usage. Promising in-vitro anticancer action and binding interfaces project indole conjugates as potential leads in addressing the TNBC dilemma.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiadiazoles
/
Triple Negative Breast Neoplasms
/
Indoles
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Chem Biodivers
/
Chem. biodivers. (Online)
/
Chemistry & biodiversity (Online)
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2024
Type:
Article
Affiliation country:
India