Synthesis, 18F-radiolabeling and apoptosis inducing studies of novel 4,7-disubstituted coumarins was written by Goud, Nerella Sridhar;Kanth Makani, Venkata Krishna;Pranay, Jakkula;Alvala, Ravi;Qureshi, Insaf A.;Kumar, Pardeep;Bharath, Rose Dawn;Nagaraj, Chandana;Yerramsetty, Suresh;Pal-Bhadra, Manika;Alvala, Mallika. And the article was included in Bioorganic Chemistry in 2020.COA of Formula: C6H9ClO3 The following contents are mentioned in the article:
A new series of 4,7-disubstituted coumarin derivatives I [R1 = morpholin-4-yl, 1,2,3,4-tetrahydroisoquinolin-2-yl, 4-methylpiperidin-1-yl, etc.; R2 = cyanomethyl, (4-methoxyphenyl)methyl, (4-bromophenyl)methyl, etc.] have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds I exhibited potent growth inhibitory action against the treated cancer cell lines with an IC50 range of 10-30μM. Compound I [R1 = 4-ethoxycarbonyl-piperidin-1-yl; R2 = (4-nitrophenyl)methyl (A)] exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC50 value of 7.45 ± 0.03μM, 8.95 ± 0.17μM resp. Further, the target compound A was radiolabeled with fluorine-18 [18F] to be used as a novel PET radiotracer for imaging of tumors via targeting galectin-1, using appropriate reaction conditions in the GE Tracer-lab FX2N synthesis module. The purification of the [18F] radiolabeled compound II was successfully achieved with 60% ethanol. The radiochem. purity was >85% and residual solvent limit of DMF was 65 ± 3 ppm as analyzed by HPLC, TLC & GC anal. methods. The apoptosis studies confirm the inhibition of cell proliferation with morphol. changes like cell shrinkage, blebbing and cell wall deformation, increasing the ROS levels, and loss of mitochondrial membrane potential by Acridine orange/Ethidium bromide staining, Hoechst-33342 staining, H2DCFDA staining, annexin V-FITC/PI, and JC-1 staining methods. In flow cytometric anal., the sub-G1 phase of the cell cycle is selectively arrested in a dose-dependent manner. In Gal-1 ELISA studies, compound A efficiently reduced the levels of Gal-1 protein in dose-dependent manner with an IC50 value of 100μM. The binding constant (Ka) of A with Gal-1 was observed as 1.3 × 104 M-1 by fluorescence spectroscopy. The mol. docking studies clearly showed possible interactions and the pharmacokinetic (ADMET) properties of compound A with Gal-1. The novel 4,7-disubstituted coumarins I could be a potential cytotoxic and PET imaging agents via Gal-1. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3COA of Formula: C6H9ClO3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organochlorines stimulate the central nervous system and cause convulsions, tremor, nausea, and mental confusion. Examples are dichlorodiphenyltrichloroethane (DDT), chlordane, lindane, endosulfan, and dieldrin. Organochlorine compounds are lipophylic, meaning they are more soluble in fat than in water. This gives them a high tenancy to accumulate in the food chain (biomagnification).COA of Formula: C6H9ClO3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics