Bis-pharmacophore of cinnamaldehyde-clubbed thiosemicarbazones as potent carbonic anhydrase-II inhibitors

Abstract

Here, we report the synthesis, carbonic anhydrase-II (CA-II) inhibition and structure–activity relationship studies of cinnamaldehyde-clubbed thiosemicarbazones derivatives. The derivatives showed potent activities in the range of 10.3 ± 0.62–46.6 ± 0.62 µM. Among all the synthesized derivatives, compound 3n (IC50 = 10.3 ± 0.62 µM), 3g (IC50 = 12.1 ± 1.01 µM), and 3h (IC50 = 13.4 ± 0.52 µM) showed higher inhibitory activity as compared to the standard inhibitor, acetazolamide. Furthermore, molecular docking of all the active compounds was carried out to predict their behavior of molecular binding. The docking results indicate that the most active hit (3n) specifically mediate ionic interaction with the Zn ion in the active site of CA-II. Furthermore, the The199 and Thr200 support the binding of thiosemicarbazide moiety of 3n, while Gln 92 supports the interactions of all the compounds by hydrogen bonding. In addition to Gln92, few other residues including Asn62, Asn67, The199, and Thr200 play important role in the stabilization of these molecules in the active site by specifically providing H-bonds to the thiosemicarbazide moiety of compounds. The docking score of active hits are found in range of − 6.75 to − 4.42 kcal/mol, which indicates that the computational prediction correlates well with the in vitro results.

Enzyme inhibition, molecular docking, and density functional theory studies of new thiosemicarbazones incorporating the 4‐hydroxy‐3,5‐dimethoxy benzaldehyde motif

“…hCA I, and hCA II; and AChE (Table 6). In the literature, Rasool et al [41] reported the synthesis of new thiosemicarbazones derived from 4-(dimethylamino)cinnamaldehyde which are powerful CA-II inhibitors. Additionally, molecular docking experiments were conducted to understand the atomic-level interactions of these derivatives.…”

“…Experimental and theoretical Fourier transform infrared (FT-IR) values of the compounds (cm −1 ) a Theoretical13 C NMR data of the synthesized compounds, (δ/ppm)41/58.24 150.65 153.71 126.01/105.00 131.80 148.48 186.03 CH 3 :32.38 -63.44/58.24 150.67 153.50 126.01/104.90 131.80 148.34 184.69 CH 2 : 44.53 CH 3 : 13.84 -63.40/58.26 150.99 153.73 126.14/105.20 131.50 148.90 184.27 CH 2 : 51.66 CH═: 144.83 ═CH 2 : 122.94 -63.36/58.24 151.00 153.91 126.25/105.17 131.30 148.93 185.13 CH 2 : 5241/58.25 150.53 153.55 126.06/104.91 131.63 148.27 183.30 53.70, 32.0, 29.95, 24.08, 23.52, 22.67 (cyclohexyl carbons)…”

Novel Coumarin‐Pyrazole‐Thiazoles Hybrids: Synthesis, Anticancer Activity, Molecular Docking and In Silico ADMET prediction Studies

“…Our ongoing research on discovering and developing new anticancer agents [39][40][41][42][43] is fueled by the exciting findings of coumarin derivatives with anticancer potential (as discussed previously). In this view, we present here design and synthesis of a novel series of molecular structures incorporating coumarin, pyrazole and thiazole rings in different configurations forms.…”

Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

“…Research teams worldwide are currently dedicated to designing and developing novel categories of α-glucosidase inhibitors, with a particular emphasis on heterocycle-based α-glucosidase inhibitors that have garnered increased interest in recent years. [9][10][11][12][13][14][15][16][17][18] Various heterocyclic compounds have been found to show antidiabetic properties by acting as α-glucosidase inhibitors. [19][20][21][22][23] Chromone, known as a class of natural drugs, characterized by a benzoannelated γ-pyrone ring, exhibited the potential to behave as a privileged scaffold for the development of novel molecules in the development of new drugs.…”