Search
New 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-N-(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation
Abstract
In the search for new compounds with antitumor activity, new potential anticancer agents were designed as molecular hybrids containing the structures of a triazine ring and a sulfonamide fragment. Applying the synthesis in solution, a base of new sulfonamide derivatives 20–162 was obtained by the reaction of the corresponding esters 11–19 with appropriate biguanide hydrochlorides. The structures of the compounds were confirmed by spectroscopy (IR, NMR), mass spectrometry (HRMS or MALDI-TOF/TOF), elemental analysis (C,H,N) and X-ray crystallography. The cytotoxic activity of the obtained compounds toward three tumor cell lines, HCT-116, MCF-7 and HeLa, was examined. The results showed that some of the most active compounds belonged to the R1 = 4-trifluoromethylbenzyl and R1 = 3,5-bis(trifluoromethyl)benzyl series and exhibited IC50 values ranging from 3.6 μM to 11.0 μM. The SAR relationships were described, indicating the key role of the R2 = 4-phenylpiperazin-1-yl substituent for the cytotoxic activity against the HCT-116 and MCF- 7 lines. The studies regarding the mechanism of action of the active compounds included the assessment of the inhibition of MDM2-p53 interactions, cell cycle analysis and apoptosis induction examination. The results indicated that the studied compounds did not inhibit MDM2-p53 interactions but induced G0/G1 and G2/M cell cycle arrest in a p53-independent manner. Furthermore, the active compounds induced apoptosis in cells harboring wild-type and mutant p53. The compound design was conducted step by step and assisted by QSAR models that correlated the activity of the compounds against the HCT-116 cell line with molecular descriptors.
Citations
-
2
CrossRef
-
0
Web of Science
-
2
Scopus
Authors (8)
-
Beata Żołnowska
-
Krzysztof Szafrański dr
-
Ryszard Konopiński
-
Ewa A. Grzybowska
-
Jarosław Sławiński
-
Anna Kawiak
Cite as
Full text
- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms23137178
- License
-
open in new tab
Keywords
Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 23,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2022
- Bibliographic description:
- Tomorowicz Ł., Żołnowska B., Szafrański K., Chojnacki J., Konopiński R., Grzybowska E. A., Sławiński J., Kawiak A.: New 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-N-(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 23,iss. 13 (2022), s.7178-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms23137178
- Sources of funding:
-
- COST_FREE
- Verified by:
- Gdańsk University of Technology
seen 68 times
Recommended for you
Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives
- B. Żołnowska,
- J. Sławiński,
- Z. Brzozowski
- + 5 authors
Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability
- B. Żołnowska,
- J. Sławiński,
- A. Pogorzelska
- + 7 authors
Novel 2-alkythio-4-chloro-N-[imino(heteroaryl)methyl]benzenesulfonamide Derivatives: Synthesis, Molecular Structure, Anticancer Activity and Metabolic Stability
- B. Żołnowska,
- J. Sławiński,
- M. Belka
- + 3 authors
Synthesis, molecular structure, and metabolic stability of new series of N' -(2-alkylthio-4-chloro-5-methylbenzenesulfonyl)-1-(5-phenyl-1 H -pyrazol-1-yl)amidine as potential anti-cancer agents
- A. Pogorzelska,
- J. Sławiński,
- A. Kawiak
- + 6 authors