New thiazacridine agents: Synthesis, physical and chemical characterization, and in vitro anticancer evaluation

Abstract

<jats:p> A series of new thiazacridine agents were synthesized and evaluated as antitumor agents, in terms of not only their cytotoxicity but also their selectivity. The cytotoxicity assay confirmed that all compounds showed cytotoxic activity and selectivity. The new compound, 3-acridin-9-ylmethyl-5-(5-bromo-1 H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/AA29 – 7a), proved to be the most promising compound as it presents lower half-maximal inhibitory concentration (IC<jats:sub>50</jats:sub>) values (ranging from 0.25 to 68.03 µM) depending on cell lineage. In HepG2 cells, the lowest IC<jats:sub>50</jats:sub> value was exhibited by 3-acridin-9-ylmethyl-5-(4-piperidin-1-yl-benzylidene)-thiazolidine-2,4-dione (LPSF/AA36 – 7b; 46.95 µM). None of the synthesized compounds showed cytotoxic activity against normal cells (IC<jats:sub>50</jats:sub> &gt; 100 µM). The mechanism of death induction and cell cycle effects was also evaluated. Flow cytometric analysis revealed that the compounds LPSF/AA29 – 7a and LPSF/AA36 – 7b significantly increased the percentage of apoptotic cells and induced G2/M arrest in the cell cycle progression. Therefore, these new thiazacridine derivatives constitute promising antitumor agents whose cytotoxicity and selectivity properties indicate they have potential to contribute to or serve as a basis for the development of new cancer drugs in the future. </jats:p>

Pyronaridine: An update of its pharmacological activities and mechanisms of action

“…[89,90] Amsacrine and related anilino-acridine continue to serve as model scaffold for the design of antitumor agents. [91][92][93] Amsacrine also presents an antimalarial activity, which presumably arises in part from its DNA binding capacity. [94] Quinacrine also displays anti-cancer properties and its repurposing as an antitumor drug has been proposed, owing to its synergistic action with different drugs, such as cisplatin.…”

Synthesis and biological activities of new phthalimide and thiazolidine derivatives

“…This is one important strategy used by Medicinal Chemistry to obtain more powerful, effective, and safer drugs [5]. This strategy aims to link two or more pharmacophoric groups with good biological activities, already reported, creating a new chemical entity with the intention to increase its biological activities to combat various diseases [6,7].…”

“…The series of reagents, intermediate products called IPs (6a-c), produced for the realization of our final compounds had their methodology approved and with promising results [6,27]. In conclusion, the evaluation of new agents is necessary in order to find more selective and efficient treatments for different tumor types [28].…”

Design, Synthesis and Biological Activities of New Phthalimide and Thiazolidine Derivatives

“…Synthesis of new drugs is the combination of distinct pharmacophoric nuclei in a chemical entity, which is termed as molecular hybridization, which is one of the important strategies used by Medicinal Chemistry to obtain more powerful, effective and safer drugs [5]. This strategy aims to link two or more pharmacophoric groups with good biological activities, already reported, creating a new chemical entity with the intention to increase its biological activities to combat various diseases [6,7].…”

“…The series of reagents, intermediate products called IPs (6a-c), produced for the realization of our nal compounds had their methodology approved and with promising results [27,6]. In conclusion, the evaluation of new agents is necessary in order to nd more selective and e cient treatments for different types of tumors [28].…”