Synthesis and biological evaluation of new 3-amino-2-azetidinone derivatives as anti-colorectal cancer agents

Abstract

Several synthetic combretastatin A4 () derivatives were recently prepared to increase the drug efficacy and stability of the natural product isolated from the South African tree . A group of ten 3-amino-2-azetidinone derivatives, as combretastatin A4 analogues, was selected through docking experiments, synthesized and tested for their anti-proliferative activity against the colon cancer SW48 cell line. These molecules, through the formation of amide bonds in position 3, allow the synthesis of various derivatives that can modulate the activity with great resistance to hydrolytic conditions. The cyclization to obtain the 3-aminoazetidinone ring is highly diastereoselective and provides a biologically active isomer under mild reaction conditions with better yields than the 3-hydroxy-2-azetidinone synthesis. All compounds showed IC values ranging between 14.0 and 564.2 nM, and the most active compound showed inhibitory activity against tubulin polymerization , being a potential therapeutic agent against colon cancer.

Design, Synthesis, and Anticancer Activity of Novel Trimethoxyphenyl-Derived Chalcone-Benzimidazolium Salts

“…In addition, the trimethoxyphenyl group is a well-known fragment in some natural tubulin polymerization inhibitors, − such as CA-4, colchicine, and podophyllotoxin (Figure ). The 3,4,5-trimethoxyphenyl group can be linked to another aromatic system and is the only well-defined pharmacophore for the inhibition of tubulin polymerization …”

“…25 Studies on molecular targets and docking calculations suggested that these imidazolium salt hybrids may be mammalian target of rapamycin (mTOR) signaling inhibitors. 25−27 In addition, the trimethoxyphenyl group is a well-known fragment in some natural tubulin polymerization inhibitors, 30−32 such as CA-4, 30 colchicine, 31 and podophyllotoxin 32 (Figure 1). The 3,4,5-trimethoxyphenyl group can be linked to another aromatic system and is the only well-defined pharmacophore for the inhibition of tubulin polymerization.…”

Antitumor Activity of New Chemical Compounds in Triple Negative Mammary Adenocarcinoma Models

“…Two of the selected compounds are β-lactams: PGC22i is a penicillin and CIT171B3 is a monobactam. Both, penicillin compounds [9,17,21] and monobactams [22][23][24], have demonstrated antitumor activity.…”

Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells

“…Furthermore, drug resistance remains a challenge, leading to the failure of CRC treatment ( 4 ). In addition to gaining an understanding of the mechanism of intrinsic and acquired therapy resistance, researchers have focused on small-molecule compounds that induce less toxicity and have greater efficacy for cancer treatment ( 5 , 6 ). In our previous study, a chemical library obtained from ChemBridge Corporation was screened for potential novel anticancer agents.…”