Design and synthesis of substituted dihydropyrimidinone derivatives as cytotoxic and tubulin polymerization inhibitors was written by Sana, Sravani;Tokala, Ramya;Bajaj, Deepti Madanlal;Nagesh, Narayana;Bokara, Kiran Kumar;Kiranmai, Gaddam;Lakshmi, Uppu Jaya;Vadlamani, Swapna;Talla, Venu;Shankaraiah, Nagula. And the article was included in Bioorganic Chemistry in 2019.Electric Literature of C6H9ClO3 The following contents are mentioned in the article:
An operationally simple Biginelli protocol was employed for the synthesis of new C6-carbon based aryl α-haloacrylamide-linked dihydropyrimidinone derivatives I (R = H, NHC(O)C(=CH2)Br; R1 = NHC(O)C(=CH2)Br, Cl; R2 = Ph, thiophen-2-yl, 4-phenylphenyl, etc.). The synthesized compounds were appraised for their in vitro antiproliferative potential against a selected panel of human cancer cell lines especially MCF-7 (human breast cancer), MDA-MB-231 (human breast cancer), HCT-116 (human colon cancer), HCT-15 (human colorectal adenocarcinoma), HT-29 (human colon adenocarcinoma) and DU145 (human prostate cancer) along with normal lung fibroblasts (HFL-1). Preferably, compounds containing α-haloacrylamide I functionality were found to exhibit most significant cytotoxicity (IC50 value 0.54 ± 0.12 to 8.35 ± 0.82 μM) against the listed cancer cell lines, particularly towards breast cancer cell lines MCF-7 and MDA-MB-231 (IC50 value 0.54 ± 0.12 to 3.70 ± 0.24 μM). In the seam of synthesized compounds, compound I (R = H; R1 = NHC(O)C(=CH2)Br; R2 = 4-methylphenyl (A)) exhibited potent antiproliferative activity against breast cancer cell lines namely MCF-7 (IC50 value 0.54 ± 0.12 μM) and MDA-MB-231 (IC50 value 1.18 ± 0.32 μM). Further to understand the underlying apoptosis mechanisms, different staining techniques such as AO/EB, DCFDA, and DAPI staining were performed. To know the extent of apoptosis and loss of mitochondrial membrane potential in MCF-7 cell lines, annexin V-FITC/PI and JC-1 were performed. Cell cycle anal. revealed that compound (A) arrested the cells at G2/M phase in a dose-dependent manner. The compound (A) also found to exhibit significant inhibition of tubulin polymerization (IC50 of 6.91 ± 0.43 μM) with microtubule destabilizing properties. Mol. docking studies also revealed that compound (A) efficiently interacted with critical catalytically active residues Ser178, Val238, and Val318 of the α/β-tubulin by a hydrogen bond. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Electric Literature of 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. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Electric Literature of C6H9ClO3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics