New halogenated chalcones with cytotoxic and carbonic anhydrase inhibitory properties: 6‐(3‐Halogenated phenyl‐2‐propen‐1‐oyl)‐2(3H)‐benzoxazolones

Abstract

In this study, novel halogenated chalcones, 6-(3-halogenated phenyl-2-propen-1-one)-2(3H)-benzoxazolones (2a-n), were synthesized for the first time (except 2a), and their chemical structures were characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR, and high-resolution mass spectrometry spectra. Cytotoxic activities and carbonic anhydrase (CA) inhibitory effects of the compounds were studied to identify new possible drug candidate molecules. Cytotoxicity results pointed out that compound 2m, 6-[3-(3-bromophenyl)-2-propenoyl]-2(3H)-benzoxazolone, had the highest cytotoxicity (CC 50 ) and potency selectivity expression (PSE) values. Thus, compound 2m can be considered as a lead compound of the series in terms of cytotoxicity. When the CA inhibition results of the compounds were evaluated, it was found that the K i values of the compounds ranged from 30.5 ± 11.3 to 65.5 ± 25.6 µM toward hCA I, and they ranged from 7.3 ± 1.8 to 58.8 ± 12.3 µM toward hCA II. However, the K i values of the reference drug, acetazolamide (AZA), were 30.2 ± 7.8 and 4.4 ± 0.6 μM toward hCA I and hCA II, respectively. According to the results obtained, compounds 2a-n had lower K i values than AZA, whereas compounds 2a, 2b, 2e-g, 2l, and 2n had similar K i values, compared with AZA. So, the compounds 2a, 2b, 2e-g, 2l, and 2n can be considered as lead molecules of this series for further considerations.

Synthesis and in silico studies of triazene‐substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors

“…CA inhibition assay was performed as described in our previous studies. [ 27,38,54–59 ] hCA I and II isoenzymes were purified from human erythrocytes by Sepharose‐4B‐ l ‐tyrosine‐sulfanilamide affinity chromatography. [ 60 ] Sepharose‐4B‐ l ‐tyrosine‐sulfanilamide was used as an affinity matrix for selective retention of both hCA isoenzymes.…”

Novel Mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(aminomethyl)-6-{3-[4-(trifluoromethyl)phenyl]acryloyl}-2(3H)- benzoxazolones

“…CA inhibition assay was recorded according to previous studies [4,10,27,49,[60][61][62][63][64]. The hCA I and II isoenzymes were purified from human red blood cells by sepharose-4B-L-tyrosine-sulfanilamide affinity chromatography [65], which was used as an affinity matrix for selective retention of both hCA isoenzymes [27,66].…”

“…The compounds 1 and 1a-g were synthesized successfully for the first time (except 1 and 1g) [27,71] according to Figure 2. First, the chalcone compound 1, 6-[3-(4-trifluoromethylphenyl)-2-propenoyl]-2(3H)-benzoxazolone, was synthesized according to our previous study [27] by the classical Claisen-Schmidt reaction realized between 4-trifluorobenzaldehyde and 6-acetyl-2(3H)-benzoxazolone [10,27]. In the second step, the Mannich bases were synthesized by the Mannnich reaction of compound 1 with suitable seconder amines.…”

“…The design of drugs bearing chalcones is often used in medicinal chemistry due to their several bioactivities such as antiinflammatory [19], antifungal [20,21], antimalarial [22,23], antimicrobial [24], anticancer [25,26], cytotoxic [10,27], antioxidant [28,29], carbonic anhydrase inhibiting [10,27,30], acetylcholinesterase inhibiting [31][32][33][34], and antidiabetic [35,36] activities. In our previous studies, we synthesized a series of benzoxazolone containing chalcone compounds and evaluated their cytotoxic and CA-inhibiting activities [27].…”

Hydroxamates as a potent skeleton for the development of metallo‐β‐lactamase inhibitors

“…The toxicity of hydroxamates was evaluated as previously reported (Bilginer et al, 2020;Günsel et al, 2020; Liu Tugrak et al, 2020), inhibitor 5 with a working concentration ranging from 0 to 800 μM was subjected to a cytotoxicity assay using human breast cancer cells (MCF-7). It can be seen in Figure 9 that, when the concentration of 5 is up to 200 μM, the cell survival rate remains above 80%, indicating that the hydroxamate is less cytotoxic to MCF-7 cells.…”