Drs. Bessette and Kinch reply

Bessette, Louis; Kinch, C.

doi:10.3899/jrheum.220909

Cited by 1 publication

(1 citation statement)

References 12 publications

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“…The human glioblastoma cell line, U87 (kind gift from Dr. Kirsi Granberg, Faculty of Medicine and Health Technology, Tampere, Finland) and the non-cancer cell, mouse embryonic fibroblast cell line (MEF, gifted by Prof. Pasi Kallio, Faculty of Medicine and Health Technology, Tampere, Finland) were selected for this study as they overexpress TrkA receptor protein [29,30]. These cells were grown in DMEM supplemented with 10% FBS and were used to investigate the anticancer effect of benzenesulfonamide derivatives.…”

Section: Cell Culturementioning

confidence: 99%

Benzenesulfonamide Analogs: Synthesis, Anti-GBM Activity and Pharmacoprofiling

Murugesan,

Konda Mani,

Thiyagarajan

et al. 2023

IJMS

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The tropomyosin receptor kinase A (TrkA) family of receptor tyrosine kinases (RTKs) emerge as a potential target for glioblastoma (GBM) treatment. Benzenesulfonamide analogs were identified as kinase inhibitors possessing promising anticancer properties. In the present work, four known and two novel benzenesulfonamide derivatives were synthesized, and their inhibitory activities in TrkA overexpressing cells, U87 and MEF cells were investigated. The cytotoxic effect of benzenesulfonamide derivatives and cisplatin was determined using trypan blue exclusion assays. The mode of interaction of benzenesulfonamides with TrkA was predicted by docking and structural analysis. ADMET profiling was also performed for all compounds to calculate the drug likeness property. Appropriate QSAR models were developed for studying structure–activity relationships. Compound 4-[2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfon-amide (AL106) and 4-[2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)hydrazinyl]-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide (AL107) showed acceptable binding energies with the active sites for human nerve growth factor receptor, TrkA. Here, AL106 was identified as a potential anti-GBM compound, with an IC50 value of 58.6 µM with a less toxic effect in non-cancerous cells than the known chemotherapeutic agent, cisplatin. In silico analysis indicated that AL106 formed prominent stabilizing hydrophobic interactions with Tyr359, Ser371, Ile374 and charged interactions with Gln369 of TrkA. Furthermore, in silico analysis of all benzenesulfonamide derivatives revealed that AL106 has good pharmacokinetics properties, drug likeness and toxicity profiles, suggesting the compound may be suitable for clinical trial. Thus, benzenesulfonamide analog, AL106 could potentially induce GBM cell death through its interaction with TrkA and might be an attractive strategy for developing a drug targeted therapy to treat glioblastoma.

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Section: Cell Culturementioning

confidence: 99%