Design, Synthesis, Biological and Computational Assessment of New Thiazolidin‐4‐one Derivatives as Potential Anticancer Agents Through the Apoptosis Pathway

Abstract

A variety of novel thiazolidin‐4‐one himachalene derivatives were designed and synthesized through hetero‐cyclization of thiosemicarbazone analogs that have previously exhibited strong anticancer activity. The synthesized products 2 a–4 f were completely characterized by 1H NMR, 13C NMR, IR, and HRMS and were later submitted for in vitro evaluation of their anticancer activity and cytotoxicity on a panel of four human cancer cell lines ( i.eHT‐1080, MCF‐7, A‐549, and MDA‐MB‐231). Most of the evaluated compounds showed potent antiproliferative activities against the four human cancer cell lines with tested IC50 values ranging from 5.25±0.32 to 9.26±0.73 μM. The mechanism of action revealed that compounds 2 b and 4 b induced caspase‐3/7‐activated apoptosis and cell cycle arrest in the G0/G1 stage in HT‐1080 and A‐549 cells. Furthermore, molecular docking studies were conducted to evaluate the binding affinities and the possible binding modes of the top‐performing compounds 2 b and 4 b. This was later supported by Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis predicting their prospective pharmacological profiles. The outcome of this study supports the validity of our strategy and presents 2 b and 4 b as a pattern for the discovery of novel cancer therapeutics.

Design, Synthesis, Cytotoxic Effect Evaluation and Molecular Docking of (R)‐Camphor‐Based Thiazolidinone‐Isoxazole and Thiazolidinone‐1,2,3‐triazole Hybrids“

“…Cell culture was realized in a manner analogous to [35–37] . The human fibrosarcoma cell line HT‐1080 (CCL 121) was purchased from Sigma Aldrich (ECACC collection, Saint Quentin Fallavier, France).…”

“…Cell culture was realized in a manner analogous to. [35][36][37] The human fibrosarcoma cell line HT-1080 (CCL 121) was purchased from Sigma Aldrich (ECACC collection, Saint Quentin Fallavier, France). The human breast adenocarcinoma MCF-7 (HTB-22) and lung carcinoma A-549 (CCL-185) cell lines were purchased from the American Type Culture Collection (ATCC).…”

Synthesis, Characterization, Molecular Docking and in vitro Biological Studies of Thiazolidin‐4‐one Derivatives as Anti‐Breast‐Cancer Agents

“…Overexpression of VEGFR1 has been associated with a poor prognosis, as it is thought to contribute to tumor growth and metastasis. [11] Thiazolidin-4-one and its derivatives have a wide range of pharmacological activities such as anticancer [12][13][14][15][16][17] anti-inflammatory, analgesic, anticonvulsant, antimicrobial, local and spinal anesthetics, central nervous system stimulants, hypnotics, anti-HIV, antidiabetic, follicle-stimulating hormone receptor antagonist. [18][19][20][21][22] The aim of this study is to develop new and effective anticancer agents through the synthesis of thiazolidin-4-one derivatives of 4-furfuryloxy-benzohydrazide.…”

“…Thiazolidin‐4‐one and its derivatives have a wide range of pharmacological activities such as anticancer [12–17] anti‐inflammatory, analgesic, anticonvulsant, antimicrobial, local and spinal anesthetics, central nervous system stimulants, hypnotics, anti‐HIV, antidiabetic, follicle‐stimulating hormone receptor antagonist [18–22] …”