New four 3,6-bis(alkylamino)ureidoacridines were synthesized and thoroughly characterized using NMR spectra. In vitro DNA binding studies of acridines carried out employing absorption, fluorescence ...and circular dichroism measurements revealed their binding into DNA via intercalation. The UV–Vis absorbance data were analysed to obtain the binding constant (
K
b
).
K
b
values were found in the range of 4.46 − 6.73 × 10
4
M
−1
. The DNA viscosity measurements were also performed to confirm the binding mode of the investigated acridines.
Graphical abstract
This study focuses on the synthesis and structural characterization of new compounds that integrate thiazolidine-2,4-dione, acridine moiety, and an acetamide linker, aiming to leverage the ...synergistic effects of these pharmacophores for enhanced therapeutic potential. The newly designed molecules were efficiently synthesized through a multi-step process and subsequently transformed into their hydrochloride salts. Comprehensive spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and elemental analysis, were employed to determine the molecular structures of the synthesized compounds. Biological evaluations were conducted to assess the therapeutic potential of the new compounds. The influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. An in-depth analysis of the structure–activity relationship (SAR) revealed intriguing insights into their cytotoxic profiles. Compounds with electron-withdrawing groups generally exhibited lower IC50 values, indicating higher potency. The presence of the methoxy group at the linking phenyl ring modulated both the potency and selectivity of the compounds. The variation in the acridine core at the nitrogen atom of the thiazolidine-2,4-dione core significantly affects the activity against cancer cell lines, with the acridin-9-yl substituent enhancing the compounds’ antiproliferative activity. Furthermore, compounds in their hydrochloride salt forms demonstrated better activity against cancer cell lines compared to their free base forms. Compounds 12c·2HCl (IC50 = 5.4 ± 2.4 μM), 13d (IC50 = 4.9 ± 2.9 μM), and 12f·2HCl (IC50 = 4.98 ± 2.9 μM) demonstrated excellent activity against the HCT116 cancer cell line, and compound 7d·2HCl (IC50 = 4.55 ± 0.35 μM) demonstrated excellent activity against the HeLa cancer cell line. Notably, only a few tested compounds, including 7e·2HCl (IC50 = 11.00 ± 2.2 μM), 7f (IC50 = 11.54 ± 2.06 μM), and 7f·2HCl (IC50 = 9.82 ± 1.92 μM), showed activity against pancreatic PATU cells. This type of cancer has a very high mortality due to asymptomatic early stages, the occurrence of metastases, and frequent resistance to chemotherapy. Four derivatives, namely, 7e·2HCl, 12d·2HCl, 13c·HCl, and 13d, were tested for their interaction properties with BSA using fluorescence spectroscopic studies. The values for the quenching constant (Ksv) ranged from 9.59 × 104 to 10.74 × 104 M−1, indicating a good affinity to the BSA protein.
A series of novel Ga(III)—pyridine carboxylates (Ga(Pic)
3
·H
2
O (GaPic; HPic = picolinic acid), H
3
OGa(Dpic)
2
·H
2
O (GaDpic; H
2
Dpic = dipicolinic acid), Ga(Chel)(H
2
O)(OH)
2
·4H
2
O (GaChel; ...H
2
Chel = chelidamic acid) and Ga(Cldpic)(H
2
O)(OH)
2
(GaCldpic; H
2
Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H
2
Dpic systems by potentiometry and
1
H NMR spectroscopy and mononuclear complex species were determined; Ga(Pic)
2
+
(log
β
021
= 16.23(6)), Ga(Pic)
3
(log
β
031
= 20.86(2)), Ga(Dpic)
2
−
(log
β
021
= 15.42(9)) and Ga(Dpic)
2
(OH)
2−
(log
β
-121
= 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale
1
H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC
50
(0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant
P. aeruginosa
. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.
Graphical abstract
Three silver(I) dipeptide complexes Ag(GlyGly)
(NO
)
(AgGlyGly), Ag
(GlyAla)(NO
)
(AgGlyAla) and Ag
(HGlyAsp)(NO
)
(AgGlyAsp) were prepared, investigated and characterized by vibrational ...spectroscopy (mid-IR), elemental and thermogravimetric analysis and mass spectrometry. For AgGlyGly, X-ray crystallography was also performed. Their stability in biological testing media was verified by time-dependent NMR measurements. Their in vitro antimicrobial activity was evaluated against selected pathogenic microorganisms. Moreover, the influence of silver(I) dipeptide complexes on microbial film formation was described. Further, the cytotoxicity of the complexes against selected cancer cells (BLM, MDA-MB-231, HeLa, HCT116, MCF-7 and Jurkat) and fibroblasts (BJ-5ta) using a colorimetric MTS assay was tested, and the selectivity index (SI) was identified. The mechanism of action of Ag(I) dipeptide complexes was elucidated and discussed by the study in terms of their binding affinity toward the CT DNA, the ability to cleave the DNA and the ability to influence numbers of cells within each cell cycle phase. The new silver(I) dipeptide complexes are able to bind into DNA by noncovalent interaction, and the topoisomerase I inhibition study showed that the studied complexes inhibit its activity at a concentration of 15 μM.
Indole-based chalcones have been identified as interesting compounds with anticancer properties. In the present study, we report the synthesis and evaluation of new 1-methoxyindole and 2-alkoxyindole ...chalcone hybrids as antiproliferative agents active against colorectal carcinoma cell line. Among the 19 investigated molecules, four inhibit the proliferation of colorectal cancer cells HCT-116 with IC
50
values <8 µM and display low cytotoxicity to fibroblast cell line 3T3. The UV–visible, CD and fluorescence competitive displacement assays with ethidium bromide and Hoechst 33258 performed with two active chalcones demonstrated that investigated chalcones interact with calf thymus (CT) DNA through the groove binding mode. Likewise, the quenching interaction of chalcones with bovine serum albumin (BSA) was studied in vitro under optimal physiological condition (pH = 7.4). The Stern–Volmer constant for chalcone-BSA system was found in the range of 10
5
M
−1
.
Two series of novel chalcone derivatives containing acridin-9-yl or acridin-4-yl moiety have been synthesized, structure elucidated and further evaluated for their growth inhibitory activity against ...human cancer cell lines. Among the 12 investigated molecules, (2
E
)-3-(acridin-4-yl)-1-(3,4,5-trimethoxyphenyl)-prop-2-en-1-one (
4e
) exerted the best cytotoxic activity against aggressive and invasive, triple-negative breast cancer cell line MDA-MB-231 and estrogen responsive MCF-7 cells with the IC
50
values of 8.4 and 7.7 μM respectively and was selected for further studies. Furthermore, flow cytometry analysis showed
4e
-induced, cell cycle block in the G2/M phase with a concomitant increase in the number of cells with sub-G0/G1 content, which is considered as a marker of apoptosis. Thereafter, we evaluated that compound
4e
induced cell death by mitochondria-mediated apoptosis associated with loss of mitochondrial membrane potential (MMP), dysregulation of Bax and Bcl-xl protein expression, cytochrome
c
release, caspase 7 activation, and PARP cleavage. In addition, upregulation of p53 and p21 has also been observed. In vitro DNA interaction studies demonstrated that
4e
interacts with CT DNA by bimodal binding mode: intercalation and groove-binding. Chalcone
4e
showed an affinity to bovine serum albumin that indicates that can be efficiently transported by serum proteins in the bloodstream. This evidence fully confirmed that compound
4e
could be a potential candidate that deserves further development as an antitumor agent against breast cancer.
Graphical abstract
This review describes the synthesis of a wide range of novel tetrahydroacridine derivatives (tiocyanates, selenocyanates, ureas, selenoureas, thioureas, isothioureas, disulfides, diselenides and ...several tacrine homo‐ and hetro‐hybrids). These tacrine congeners exhibit significant anticholinesterase and cytotoxic properties and may therefore be of considerable potential for the development of new drugs for the treatment of Alzheimer's disease.
This review describes the synthesis of a wide range of novel tetrahydroacridine derivatives. These tacrine congeners exhibit significant anticholinesterase and cytotoxic properties and may therefore be of considerable potential for the development of new drugs for the treatment of Alzheimer's disease.
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•New spiro acridin-isoxazolines were synthesized by 1,3-dipolar cycloaddition.•Single crystal X-ray structure of spiroacridine derivative 5a was solved.•Evaluation of DNA-binding ...properties by spectroscopic methods.•Topoisomerase I inhibition assay.
Eight spiroacridine derivatives containing the isoxazoline ring were synthesized and characterized using elemental analysis, IR, UV–vis, and NMR measurements. Their interactions with calf thymus DNA were extensively studied by various spectroscopic techniques and gel electrophoresis. The UV–visible and CD measurements implied that these derivatives interact with calf thymus DNA through intercalation. The Stern-Volmer quenching constants were determined and ranged from 0.126×104 to 1.394×104M−1. A topoisomerase I inhibition assay was performed with the spiroacridine derivatives.
Four novel zinc complexes were prepared and characterized by infrared spectroscopy, elemental and thermal analysis and single-crystal X-ray structural analysis. Binding of all complexes to CT DNA was ...examined using spectral methods. Furthermore, inhibition activity towards topoisomerase I and antimicrobial activity was determined.
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Four novel Zn(II) complexes containing fenamic acid (Hfen), a precursor of non-steroidal anti-inflammatory drugs (NSAIDs), and different coligands namely methanol, N,N,N′,N′-tetramethylethylene diamine (tmen), N,N′-bis(3-aminopropyl)ethylenediamine (bapen) and 14,811-tetraazacyclotetradecane (cyclam) were prepared in crystalline form. The composition of the complexes was determined by infrared spectroscopy, elemental and thermal analyses. Results of single-crystal X-ray structure analysis have revealed that while complex 1 is composed of trinuclear Zn3(fen)6(MeOH)2 molecules, the three remaining complexes 2–4 are mononuclear with composition Zn(fen)2(tmen) (2), Zn(bapen)(fen)fen (3), and Zn(cyclam)(fen)2 (4). Binding of all prepared complexes to calf thymus DNA was investigated using UV–vis, fluorescence and circular dichroism (CD) measurements. In addition, inhibition activity of complexes against topoisomerase I along with antimicrobial activity was determined.
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