Anti-breast cancer action of carbonic anhydrase IX inhibitor 4-[4-(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-benzylidene-hydrazinocarbonyl]-benzenesulfonamide (BSM-0004): in vitro and in vivo studies

Abstract

Anti-breast cancer action of novel human carbonic anhydrase IX (hCA IX) inhibitor BSM-0004 has been investigated using in vitro and in vivo models of breast cancer. BSM-0004 was found to be a potent and selective hCA IX inhibitor with a Ki value of 96 nM. In vitro anticancer effect of BSM-0004 was analysed against MCF 7 and MDA-MA-231 cells, BSM-0004 exerted an effective cytotoxic effect under normoxic and hypoxic conditions, inducing apoptosis in MCF 7 cells. Additionally, this compound significantly regulates the expression of crucial biomarkers associated with apoptosis. The investigation was extended to confirm the efficacy of this hCA IX inhibitor against in vivo model of breast cancer. The results specified that the treatment of BSM-0004 displayed an effective in vivo anticancer effect, reducing tumour growth in a xenograft cancer model. Hence, our investigation delivers an effective anti-breast cancer agent that engenders the anticancer effect by inhibiting hCA IX.

Benzenesulfonamides with different rigidity-conferring linkers as carbonic anhydrase inhibitors: an insight into the antiproliferative effect on glioblastoma, pancreatic, and breast cancer cells

“…Moreover, in this acidic and hypoxic milieu tumour cells have been reported to gain increased genetic instability and mutagenesis rate 11 , 12 , and to become more resistant to radiation therapy and chemotherapy 13–16 . It has been amply demonstrated in several cell lines (melanoma, gastric, breast, oral, cervical, bladder, glioblastoma, pancreatic, hepatocellular, and colorectal cancer) 17–21 and in xenograft tumours in vivo 22 , 23 that selective CA IX and XII inhibitors can impair CA IX activity, triggering thus apoptosis and ferroptosis 23 .…”

Development and Evaluation of Some Molecular Hybrids of N-(1-Benzylpiperidin-4-yl)-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio) as Multifunctional Agents to Combat Alzheimer’s Disease

“…After 4 h, the medium was removed and DMSO (200 μL) was added; the formation of formazan crystals was observed, and absorbance was taken at 570 nm. Results have been represented as the mean ± standard deviation (SD) of three independent experiments ( n = 3). ,, …”

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

“…The pyrazoline derivatives consisting of carbothioamide group showed significant EGFR inhibition, showing IC 50 values ranging from 1.66 to 1.9 μM, and halted the growth of cancer cells [ 87 ]. Our previous studies also suggested that molecules from pyrazolo[3,4- d ]pyrimidine, urea, piperazine, and hybrids have shown fabulous anticancer activities via inhibition of various oncoproteins against cancers [ 87 , 88 , 89 ]. These studies may help to postulate new possibilities for developing novel small molecule drugs with effective anticancer activity.…”

“…Tyrphostin AG 1024, a selective inhibitor of IGF-1R, markedly increases the response of tumor cells to ionizing radiation [ 99 ]. Moreover, Pyrazole pyridine-peperidinyl containing propanone also showed highly antitumor potency against cancer cells growth [ 88 , 100 ]. BMS-754807 is a reversible and strong inhibitor of the IGF-1 receptor/insulin receptor family kinases with Ki = 2 nmol/L [ 101 ].…”