Diastereoselective approach to rationally design tetrahydro-β-carboline–isatin conjugates as potential SERMs against breast cancer

Abstract

A series of tetrahydro-β-carboline–isatin conjugates was prepared and assayed for anti-proliferative activities on Estrogen Responsive ER(+) and non-responsive ER(−ve) cell-lines.

Triarylethylene-indolin-2,3-dione molecular conjugates: design, synthesis, docking studies and anti-proliferation evaluation

“…Recent reports from our laboratory have disclosed the synthesis and anti-proliferative activities of ospemifene-isatin conjugates with promising results against MCF-7 cells, in contrast to the results against MDA-MB-231 cells, with the most active conjugate of the series exhibiting an IC 50 value of 1.56 mM. 22 The currently described work was a continuation and logical extension of our interests [19][20][21] and involved the use of a 1H-1,2,3-triazole core to link C-5-functionalized isatin to the alkyl side chain of ospemifene and methylated ospemifene. The use of triazole as a linker was further supported by its presence in anastrazole, an aromatase inhibitor used in BC chemotherapy.…”

Recent advances in isatin hybrids as potential anticancer agents

“…Besides the isatin hybrids mentioned above, some other hybrids also showed certain anticancer activity, such as hybrid 61a (GI 50 : 0.75–28.39 μM, SRB assay) displayed broad‐spectrum activity against a panel of cancer cell lines derived from nine different cancer types: leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers. [ 122–128 ] However, the majority of them were not superior to the references and still need to be modified.…”

Computer-Aided Ligand Discovery for Estrogen Receptor Alpha

“…A few authors have used docking to study the poses and conformations of these compounds and have found them to be potent in vivo and/or in vitro experiments or to predict their relative activity. In 2019, Sharma and colleagues used in silico docking to support the activity of their designed and synthesized tetrahydro-b-carboline-isatin conjugates with both tetrahydro-b-carboline and istatin C-1 and C-5 stereomers [201]. The most promising hit displayed an IC 50 of 37.42 µM against MCF-7 cells as opposed to 50 µM for tamoxifen and had minimal effects on ERα-MDA-MB-231 cells thus confirming that their actions are ERα mediated [201].…”

“…In 2019, Sharma and colleagues used in silico docking to support the activity of their designed and synthesized tetrahydro-b-carboline-isatin conjugates with both tetrahydro-b-carboline and istatin C-1 and C-5 stereomers [201]. The most promising hit displayed an IC 50 of 37.42 µM against MCF-7 cells as opposed to 50 µM for tamoxifen and had minimal effects on ERα-MDA-MB-231 cells thus confirming that their actions are ERα mediated [201]. The authors used Chem3D Ultra to draw their ligands and Avogadro1.2.0 tool to optimize them for docking to the UCSF Chimera prepared protein (pdb entry 3ERT) using AutoDock Vina [54,[201][202][203].…”