A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against ...four human carbonic anhydrase (
CA) isoforms. All compounds displayed nanomolar potency against the cancer-related
CA IX and
CA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic
CA I and
CA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective
CA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against
CA XII, with single-digit nanomolar
values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic
CA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies.
Diabetes mellitus (DM) stands as one of the most widespread diseases encountered today. It is primarily characterized by diminished insulin levels and heightened blood glucose concentrations. ...Inhibition of the α-amylase enzyme plays a pivotal role in the management of diabetes mellitus. Piperazine and sulfonamide groups are recognized for their extensive range of biological effects. The current study involved synthesizing five phenylsulfonyl piperazine derivatives. An evaluation of their α-amylase inhibitory capacities was conducted. Phenylsulfonyl piperazine derivatives (compounds 1-5) exhibited notable α-amylase enzymatic inhibition, with compound 4 showing the most substantial potential for inhibition. The inhibitory percentage of compound 4 (80.61±0.62) surpassed that of the standard drug acarbose (78.81±0.02). The molecular docking studies identified compound 4 as possessing the most substantial inhibitory effect on the α-amylase enzyme, with notable binding energy -8.2 kcal/mol. This compound exhibited specific interactions, including π-π stacking and π-anion interactions with key enzyme residues, solidifying its role as a potent inhibitor
Abstract Benzene sulfonamides are an important biological substituent for several activities. In this study, hybridization of benzene sulfonamide with piperazine derivatives were investigated for ...their antioxidant capacity and enzyme inhibitory potencies. Six molecules were synthesized and characterized. DPPH, ABTS, FRAP, CUPRAC, chelating and phosphomolybdemum assays were applied to evaluate antioxidant capacities. Results show that compounds have high antioxidant capacity and compound 4 has the best antioxidant activity among them. Compound 4 has higher antioxidant activity than references for FRAP (IC 50 : 0.08 mM), CUPRAC (IC 50 : 0.21 mM) and phosphomolybdenum (IC 50 : 0.22 mM) assays. Besides this, compound 4 has moderate DPPH and ABTS antioxidant capacity. Furthermore, enzyme inhibition activities of these molecules were investigated against AChE, BChE, tyrosinase, α -amylase and α -glucosidase enzymes. It was revealed that all compounds have good enzyme inhibitory potential except for α -amylase enzyme. The best inhibitory activities were observed for AChE with compound 5 the same value (IC 50 : 1.003 mM), for BChE with compounds 2 and 5 the same value (IC 50 : 1.008 mM), for tyrosinase compound 4 (IC 50 : 1.19 mM), and for α -glucosidase with compound 3 (IC 50 : 1.000 mM). Docking studies have been conducted with these molecules, and the results correlate well with the inhibitory assays.
The tandem hydroamination-annulation reaction of 4-pentyne-nitriles in the presence of amine nucleophiles and a cooperatively operating catalyst system, consisting of Ph(3)PAuCl and Zn(ClO(4))(2), ...provides an efficient route to 2-aminopyrroles. Two regioisomeric 2-aminopyrroles were formed in moderate to good yields.
Coumarins (2H‐1‐benzopyran‐2‐one), derivatives that can be isolated from several plants, have been reported for their anticoagulant, antimicrobial, anti‐inflammatory, or anticancer activity. Some of ...these structures are currently approved for the treatment of cardiovascular diseases, as antibiotics or as an anticancer drug. Given the great potential of this structure and the limited number of studies that focus on molecules derived from carbon 8 of the benzopyranone heterocycle, we synthesized in this project 38 coumarin derivatives by substituting carbon 8 of the benzopyran ring with some aromatic and aliphatically substituted piperidines and piperazines. As a few of these structures were already shown to exhibit some carbonic anhydrase (CA) inhibition and as CA enzymes are reported to be closely related to inflammation, the synthesized derivatives were evaluated for their anti‐inflammatory activity in vitro. The results indicated that compounds 20 and 31 revealed promising anti‐inflammatory activity, as they demonstrated better activity than the reference drugs.
A series of 38 coumarin (2H‐1‐benzopyran‐2‐one) derivatives was synthesized by substituting carbon 8 of the benzopyran ring with aromatic and aliphatically substituted piperidines and piperazines. The synthesized derivatives were evaluated for their anti‐inflammatory activity in vitro. The highest anti‐inflammatory activities (nitrite inhibition) were observed for compounds 20 and 31. Compounds 24 and 25 also led to a slight decrease in prostaglandin E2 synthesis.
Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular ...defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine presents some toxicity and therefore is usually supplemented in a prodrug approach. Here, some thiazolidine-4-carboxylic acids were synthesized and evaluated for their antioxidant properties via the DDPH and CUPRAC assays. Then, the cysteine releasing capacity of the obtained compounds was investigated in aqueous and organic medium in order to correlate the relevant antioxidant properties of the molecules with their cysteine releasing pattern. As a result, the structures’ antioxidative properties were not only attributed to cysteine release but also to the thiazolidine cycle itself.
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•Thiazolidine carboxylic acids were synthesized with a series of benzaldehydes.•The antioxidant activity was evaluated via the DPPH and CUPRAC assays.•The cysteine releasing pattern of each thiazolidine compound was analyzed.•The antioxidant capacity was shown to be related not only to l-cysteine release.•Thiazolidine heterocycle itself can also be considered as antioxidant.
Cancer results from unregulated cell growth. Reactivating the process of the programmed cell death, i.e. apoptosis, is a classical anticancer therapeutic strategy. The apoptosis-inducing property of ...the (2 RS ,4 R )-2-phenyl-3-propionyl-thiazolidine-4-carboxylic acid ethyl ester (ALC 67) molecule has recently been discovered. We analyzed in this study the impact of the phenyl moiety of this molecule on its biological activity by synthesizing and evaluating analogues where this substituent was replaced by a series of aromatic and aliphatic groups. The results demonstrated that the molecule's antiproliferative property resisted such modifications. Thus, in addition to developing a family of thiazolidine compounds with promising anticancer properties; our investigation revealed that the second position of the thiazolidine ring can be used either to tune the physicochemical properties of ALC67 or to introduce a fluorescent tag to the structure in order to track it in cells and determine its exact molecular mechanism of action.
The tandem hydroamination-annulation reaction of 4-pentyne-nitriles in the presence of amine nucleophiles and a cooperatively operating catalyst system, consisting of Ph
3
PAuCl and Zn(ClO
4
)
2
, ...provides an efficient route to 2-aminopyrroles. Two regioisomeric 2-aminopyrroles were formed in moderate to good yields.
The tandem hydroamination-annulation reaction of 4-pentyne-nitriles and amines with a catalyst system Ph
3
PAuCl and Zn(ClO
4
)
2
provides an efficient route to 2-aminopyrroles.
Cancer results from unregulated cell growth. Reactivating the process of the programmed cell death,
i.e.
apoptosis, is a classical anticancer therapeutic strategy. The apoptosis-inducing property of ...the (2
RS
,4
R
)-2-phenyl-3-propionyl-thiazolidine-4-carboxylic acid ethyl ester (ALC 67) molecule has recently been discovered. We analyzed in this study the impact of the phenyl moiety of this molecule on its biological activity by synthesizing and evaluating analogues where this substituent was replaced by a series of aromatic and aliphatic groups. The results demonstrated that the molecule's antiproliferative property resisted such modifications. Thus, in addition to developing a family of thiazolidine compounds with promising anticancer properties; our investigation revealed that the second position of the thiazolidine ring can be used either to tune the physicochemical properties of ALC67 or to introduce a fluorescent tag to the structure in order to track it in cells and determine its exact molecular mechanism of action.
Modification at the 2-position of the apoptosis-inducing compound ALC 67 enables tuning of its physicochemical properties.
This review describes the input of sol-gel chemistry to the immobilization of polyol dehydrogenases on electrodes, for applications in bioelectrocatalysis. The polyol dehydrogenases are described and ...their application for biosensing, biofuel cell and electrosynthesis are briefly discussed. The immobilization of proteins
sol-gel approaches is described, including a discussion on the difficulty to maintain the activity of proteins in a silica matrix and the strategies developed to offer a proper environment to the proteins by developing optimal organic-inorganic hybrid materials. Finally, the co-immobilization of the NAD
co-factor and of mediators for the elaboration of reagentless devices is presented, based on published and original data. All-in-all, sol-gel approaches appear to be a very promising for development of original electrochemical applications involving dehydrogenases in near future.
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