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Published on: February 9, 2021
Computational Search for Possible Mechanisms of 4-Thiazolidinones Anticancer Activity: The Power of Visualization
Oleg Devinyak1, Dmytro Havrylyuk2, Borys Zimenkovsky2
1Department of Pharmaceutical Disciplines, Uzhgorod National University, Narodna sq. 1, 88000 Uzhgorod, Ukraine.
Abstract:
Public databases of NCI-60 tumor cell line screen results and measurements of molecular targets in the NCI-60 panel give the opportunity to assign possible anticancer mechanism to compounds with positive outcome from antitumor assay. Here, the novel protocol of NCI databases mining where inferences are based on the visualization is presented and utilized with the aim to identify putative biological routes of 4-thiazolidinones anticancer effect. As a result, highly potent 4-thiazolidinone-pyrazoline-isatin conjugates show the similarity of activity patterns with puromycin and CBU-028 and their pattern is also highly correlated with fraction of methylated CpG sites in CD34, AF5q31 and SYK. Several compounds from this group show strong negative correlation with fraction of methylated CpG sites in HOXA5. Thiopyrano[2,3-d][1,3]thiazol-2-ones bearing naphtoquinone fragment were found to possess the same activity pattern as fusarubin does. But none of the studied 4-thiazolidinone derivatives has activity fingerprint similar to standard anticancer agents. The obtained results bring medicinal chemistry closer to the understanding of basic nature of 4-thiazolidinones effect on cancer cells.
Insights
This study reveals novel anticancer mechanisms for 4-thiazolidinone derivatives by analyzing NCI-60 data. Some compounds show promise by correlating with specific gene methylation patterns, aiding drug discovery.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Bioinformatics
Background:
- Public databases like the NCI-60 provide valuable data for understanding anticancer compound mechanisms.
- Identifying the biological pathways targeted by novel compounds is crucial for drug development.
Purpose of the Study:
- To present a novel protocol for mining NCI-60 data using visualization to identify anticancer mechanisms of 4-thiazolidinones.
- To investigate the putative biological routes of action for various 4-thiazolidinone derivatives.
Main Methods:
- Utilized a novel visualization-based protocol for NCI-60 database mining.
- Analyzed activity patterns of 4-thiazolidinone derivatives and correlated them with molecular targets and gene methylation.
- Compared activity fingerprints with known anticancer agents and related compounds.
Main Results:
- Highly potent 4-thiazolidinone-pyrazoline-isatin conjugates exhibited activity patterns similar to puromycin and CBU-028.
- These conjugates showed strong correlations with methylated CpG sites in CD34, AF5q31, and SYK, and negative correlation with HOXA5.
- Thiopyrano[2,3-d][1,3]thiazol-2-ones with a naphthoquinone fragment mirrored fusarubin's activity pattern.
- No 4-thiazolidinone derivatives displayed activity fingerprints identical to standard anticancer agents.
Conclusions:
- The study provides insights into the anticancer mechanisms of 4-thiazolidinones through data mining and pattern correlation.
- The findings contribute to a better understanding of how these compounds affect cancer cells.
- This approach aids in identifying potential therapeutic strategies and guiding future drug design in medicinal chemistry.
