Synthesis and in vitro evaluation of novel rhodanine derivatives as potential cholinesterase inhibitors

Krátký, Martin; Štěpánková, Šárka; Vorčáková, Katarína

doi:10.1016/j.bioorg.2016.07.004

Cited by 25 publications

(9 citation statements)

References 36 publications

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“…[23] Furthermore, 6-8are found to exhibit antidiabetic activities (Figure 1), particularly as aldose reductase inhibitors. [22,24,25] In the recent decades, Rhodanine acetic acid derivatives are found to be associated with antibacterial, [26,27] antifungal, [28] cholinesterase's inhibitory activity, [29] anticancer, [30] antitubercular, [31,32] antiviral [33] activities, dolichol phosphate mannose synthase (DPMS) inhibitory activities. [34] While, fluorinated compounds place an important role in medicinal chemistry with numerous advantage in terms of ADME parameters.…”

Section: Introductionmentioning

confidence: 99%

α‐Glucosidase, α‐Amylase Inhibition, Kinetics and Docking Studies of Novel (2‐Chloro‐6‐(trifluoromethyl)benzyloxy)arylidene) Based Rhodanine and Rhodanine Acetic Acid Derivatives

Kumar

Ramu

Shirahatti³

et al. 2021

ChemistrySelect

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In our effort to identify potent fluorinated small molecules as antidiabetic compounds, a novel fluorinated series of 2-chloro-6-(trifluoromethyl)benzyloxy arylidene derived Rhodanine and Rhodanine-acetic acid derivatives were synthesized and screened for α-glucosidase and α-amylase inhibitory activity. Newly synthesized compounds were characterized by 1 HNMR, 13 C NMR, and LCMS spectral data. Among the tested compounds, (Z)-5-(4-(2-chloro-6-(trifluoromethyl)benzyloxy) benzylidene)-2-thioxothiazolidin-4-one(5 a) and 2-((Z)-5-(4-(2chloro-6-(trifluoromethyl)benzyloxy)benzylidene)-4-oxo-2-thioxothiazoli-din-3-yl)acetic acid(6 a) emerged as most promising α-glucosidase inhibitors with IC 50 values 4.76 � 0.64 μM and 4.91 � 0.45 μM, respectively. Further, the kinetic inhibition experiments against yeast α-glucosidase for compounds 5 a and 6 a indicated that these are competitive inhibitors with inhibitory constant (Ki) 0.54 μg and 1.15 μg respectively.Molecular docking studies on α-glucosidase was performed by homology modelingfor the most potent compounds 5 a and 6 a to understand the putative binding mode. The study revealed substantial binding of the compounds to the active site of α-glucosidase, indicating that the position of the substituent plays a key role in its inhibitory potential.

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Section: Introductionmentioning

confidence: 99%

α‐Glucosidase, α‐Amylase Inhibition, Kinetics and Docking Studies of Novel (2‐Chloro‐6‐(trifluoromethyl)benzyloxy)arylidene) Based Rhodanine and Rhodanine Acetic Acid Derivatives

Kumar

Ramu

Shirahatti³

et al. 2021

ChemistrySelect

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“…According to the general method, the 6-chloro-isatin 2a (90.5 mg, 0.5 mmol) was utilized and the final compound 5a was obtained as a faint yellow solid compound with 85% chemical yield. 4.85 (q, J = 6.9 Hz, 1H), 4.18 (d, J = 9.4 Hz, 1H), 3.97 (q, J = 5.4 Hz, 2H), 3.82 (d, J = 6.2 Hz, 1H), 3.56 (d, J = 4.5 Hz, 4H), 3.46 (d, J = 6.0 Hz, 1H), 3.19-3.13 (m, 2H), 3.02 (q, J = 5.5 Hz, 1H), 2.77 (d, J = 7.8 Hz, 1H), 2.37-2.30 (m, 6H); 13 According to the general method, the 5-nitro-isatin 2b (96 mg, 0.5 mmol) was utilized and the final compound 5b was obtained as a faint yellow solid compound with 80% chemical yield. According to the general method, the 5-fluoro-isatin 2c (82.5 mg, 0.5 mmol) was utilized and the final compound 5c was obtained as a faint yellow solid compound with 88% chemical yield.…”

Section: General Methods For the Synthesis Of 5a-dmentioning

confidence: 99%

“…Rhodanines′ (2-thioxothiazolidin-4-ones) privileged structure has attracted much attention in pharmaceutical and medicinal chemistry [ 1 , 2 ]. These substituted rhodanines have been discovered and reported for several pharmaceutical applications, including topoisomerase II inhibition potency [ 3 ]; potential AChE inhibitors [ 4 , 5 ]; HIV-1 integrase inhibitors [ 6 ]; anti-cancer agent towards MCF-7 breast cancer cells [ 7 ] and anti-diabetic (T2DM) targeting the inhibition of enzymes such as aldose reductase (ALR) [ 8 ], α-glucosidase [ 9 ], α-amylase [ 10 ] and PTP1B enzyme [ 11 ], and other therapeutic targets have also been reported, such as antibacterial ones [ 12 ]. Chemical modification, structural elucidation and molecular interactions investigations of these compounds are still of high interest.…”

Section: Introductionmentioning

confidence: 99%

Straightforward Regio- and Diastereoselective Synthesis, Molecular Structure, Intermolecular Interactions and Mechanistic Study of Spirooxindole-Engrafted Rhodanine Analogs

et al. 2021

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Straightforward regio- and diastereoselective synthesis of bi-spirooxindole-engrafted rhodanine analogs 5a–d were achieved by one-pot multicomponent [3 + 2] cycloaddition (32CA) reaction of stabilized azomethine ylide (AYs 3a–d) generated in situ by condensation of L-thioproline and 6-chloro-isatin with (E)-2-(5-(4-chlorobenzylidene)-2,4-dioxothiazolidin-3-yl)-N-(2-morpholinoethyl)acetamide. The bi-spirooxindole-engrafted rhodanine analogs were constructed with excellent diastereo- and regioselectivity along with high chemical yield. X-ray crystallographic investigations for hybrid 5a revealed the presence of four contiguous stereocenters related to C11, C12, C19 and C22 of the spiro structure. Hirshfeld calculations indicated the presence of many short intermolecular contacts such as Cl...C, S...S, S...H, O...H, N...H, H...C, C...C and H...H interactions. These contacts played a very important role in the crystal stability. The polar nature of the 32CA reaction was studied by analysis of the conceptual DFT reactivity indices. Theoretical study of this 32CA reaction indicated that it takes place through a non-concerted two-stage one-step mechanism associated with the nucleophilic attack of AY 3a to the electrophilic ethylene derivative.

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“…Benzothiazoles and its derivatives attracted the interest of medicinal chemists because of their extensive variety of pharmacological properties, including anti-inflammatory [ 1 , 2 , 3 ], antimicrobial [ 4 , 5 , 6 , 7 ], anticancer [ 8 , 9 , 10 ], antitubercular [ 11 , 12 ], antidiabetic [ 13 ], antioxidant [ 14 , 15 ], antiviral [ 16 , 17 , 18 ], antileishmanial [ 19 ], and others [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents

Зубенко

Карцев²,

Petrou

et al. 2022

Antibiotics

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In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity. Compound 2j was found to be the most potent (MIC/MBC at 0.23–0.94 mg/mL and 0.47–1.88 mg/mL) On the other hand, compounds showed good antifungal activity (MIC/MFC at 0.06–0.47 and 0.11–0.94 mg/mL respectively) with 2d being the most active one. The docking studies revealed that inhibition of E. coli MurB and 14-lanosterol demethylase probably represent the mechanism of antibacterial and antifungal activities.

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Synthesis and in vitro evaluation of novel rhodanine derivatives as potential cholinesterase inhibitors

Cited by 25 publications

References 36 publications

α‐Glucosidase, α‐Amylase Inhibition, Kinetics and Docking Studies of Novel (2‐Chloro‐6‐(trifluoromethyl)benzyloxy)arylidene) Based Rhodanine and Rhodanine Acetic Acid Derivatives

α‐Glucosidase, α‐Amylase Inhibition, Kinetics and Docking Studies of Novel (2‐Chloro‐6‐(trifluoromethyl)benzyloxy)arylidene) Based Rhodanine and Rhodanine Acetic Acid Derivatives

Straightforward Regio- and Diastereoselective Synthesis, Molecular Structure, Intermolecular Interactions and Mechanistic Study of Spirooxindole-Engrafted Rhodanine Analogs

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents

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