Synthesis, anticancer activity, SAR and binding mode of interaction studies of substituted pentanoic acids: part II

Aim: Our previous results suggest that phenyl/naphthylacetyl pentanoic acid derivatives may exhibit dual MMP-2 and HDAC8 inhibitory activities and show effective cytotoxic properties. Methodology: Here, 13 new compounds (C1–C13) were synthesized and characterized. Along with these new compounds, 16 previously reported phenyl/napthylacetyl pentanoic acid derivatives (C14–C29) were biologically evaluated. Results: Compounds C6 and C27 showed good cytotoxicity against leukemia cell line Jurkat E6.1. The mechanisms of cytotoxicity of these compounds were confirmed by DNA deformation assay and reactive oxygen species assay. MMP-2 and HDAC8 expression assays suggested the dual inhibiting property of these two compounds. These findings were supported by results of molecular docking studies. In silico pharmacokinetic properties showed compounds C6 and C27 have high gastrointestinal absorption. Conclusion: This study highlights the action of phenyl/naphthylacetyl pentanoic acid derivatives as anticancer agents.

Natural Molecules as Talented Inhibitors of Nucleotide Pyrophosphatases/Phosphodiesterases (PDEs)

Background: Phosphodiesterases (PDEs) are a wide group of enzymes with multiple therapeutic actions, including vasorelaxation, cardiotonic, antidepressant, anti-inflammatory, antithrombotic, anti-spasmolytic, memory-enhancing, and anti-asthmatic. PDEs with eleven subtypes from PDE-1 to PDE-11 typically catalyze the cleavage of the phosphodiester bond and, hence, degrades either cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP). Objective: Several selective or non-selective inhibitors of the PDE subtypes are used clinically, i.e. sildenafil, rolipram, cysteine, etc. Recently, interest in plant-based pharmacologically bioactive compounds having potent PDEs inhibitory potential has increased. Purposely, extensive research has been carried out on natural products to explore new inhibitors of various PDEs. Therefore, this review summarizes the published data on natural PDEs inhibitors and their potential therapeutic applications. Methods: For this purpose, natural compounds with PDE inhibitory potential have been surveyed through several databases, including PubMed, Web of Sciences (WoS), Scopus, and Google Scholar. Results : According to a detailed literature survey, the most promising class of herbal compounds with PDE-inhibiting property has been found to belong to phenolics, including flavonoids (luteolin, kaempferol, icariin, etc.). Many other encouraging inhibitors from plants have also been identified, such as coumarins (23, 24) (licoarylcoumarin and glycocoumarin,), saponins ( agapanthussaponins), lignans (31, 33) [(±)-schizandrin and kobusin], terpenes (28, 29, 31) (perianradulcin A, quinovic acid, and ursolic acid), anthraquinones (18, 19) (emodin and chrysophanol), and alkaloids (Sanjoinine-D) (36). Conclusion: In this review, studies have revealed the PDE-inhibitory potential of natural plant extracts and their bioactive constituents in treating various diseases; however, further clinical studies comprising synergistic use of different therapies (synthetic & natural) to acquire multi-targeted results might also be a promising option.

UPLC-MS-Based Metabolomics Profiling for α-Glucosidase Inhibiting Property of Parkia speciosa Pods

Parkia speciosa is a food plant that grows indigenously in Southeast Asia. A great deal of interest has been paid to this plant due to its traditional uses in the treatment of several diseases. The pods contain many beneficial secondary metabolites with potential applications in medicine and cosmetics. However, studies on their phytochemical properties are still lacking. Therefore, the present study was undertaken to profile the bioactive compounds of P. speciosa pods collected from six different regions of Malaysia through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and α-glucosidase inhibitory potential. This study applied metabolomics to elucidate the differences between P. speciosa populations found naturally in the different locations and to characterize potential α-glucosidase inhibitors from P. speciosa pods. P. speciosa collected from different regions of Malaysia showed good α-glucosidase inhibitory activity, with a median inhibitory concentration (IC50) of 0.45–0.76 μg/mL. The samples from the northern and northeastern parts of Peninsular Malaysia showed the highest activity. Using UHPLC-QTOF-MS/MS analysis, 25 metabolites were identified in the pods of P. speciosa. The findings unveiled that the pods of P. speciosa collected from different locations exhibit different levels of α-glucosidase inhibitory activity. The pods are a natural source of potent antidiabetic bioactive compounds.

Permanent cardiac pacing in bradyarrhythmias: device coding

To describe different scopes of implantable pacemaker devices, a simple coding system is used. Most commonly, the first three or four letters of the pacing code are used. Letter 1 refers to the chamber(s) the pacemaker can pace: ‘A’ means atrial, ‘V’ means ventricular, while ‘D’ means dual atrial and ventricular pacing capabilities. Letter 2 refers to the chamber(s) of which the pacemaker can sense the electrical activity: ‘A’ means atrial, ‘V’ means ventricular, while ‘D’ means dual atrial and ventricular sensing properties. Single atrial or ventricular sensing/pacing is sometimes denoted as ‘S’. Letter 3 denotes the reaction of the pacemaker to a sensed event: ‘T’ means that a sensed event triggers the pacing activity of the device, ‘I’ means the inhibiting property of a sensed event to pacing the same chamber, while ‘D’ means combined triggered and inhibited functions. Letter 4 indicates the rate-responsive capabilities of the pacemaker, if any: ‘R’ shows that the pacemaker is a rate-responsive device. Following the first three or four letters, the ‘ICD’ label is used if the pacemaker is an implantable defibrillator. In case of cardiac resynchronization pacing, the abbreviation ‘CRT’ is applied: CRT-P for CRT pacemakers and CRT-D for CRT defibrillator devices.

Substituent Effect on Corrosion Inhibition of Schiff Bases Derived from Isatin

Two Schiff bases, 3-(4-hydroxyphenylimino)-1,3-dihydroindol-2-one (OPI) and 3-(4-Chloro-phenylimino)-1,3-dihydroindol-2-one (CPI) were successfully synthesized through condensation reactions giving yields of 82% and 63%, respectively. The compounds were characterized via physical and spectroscopic techniques, namely elemental analysis (C, H, N), 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy and melting point. The corrosion inhibiting property of the Schiff bases on mild steel in 1 M HCl solution was investigated by the weight loss (WL) measurements, electrochemical impedance spectroscopy (EIS) and linear polarization resistance (LPR). The concentrations of the Schiff bases were varied from 1 x 10-3 M to 1 x 10-5 M. The inhibition efficiencies obtained from all the methods employed were in good agreement where the percentage of inhibition efficiencies increased with concentration. OPI showed better inhibition efficiency than CPI with 91% highest inhibition efficiency at 1 x 10-3 M additive concentration. This is likely to be caused by the resonance donating effect due to the presence of the hydroxyl group. The adsorption behaviour obeyed Langmuir isotherm for monolayer formation.

Substituent Effect on Corrosion Inhibition of Schiff Bases Derived from Isatin

Two Schiff bases, 3-(4-hydroxyphenylimino)-1,3-dihydroindol-2-one (OPI) and 3-(4-Chloro-phenylimino)-1,3-dihydroindol-2-one (CPI) were successfully synthesized through condensation reactions giving yields of 82% and 63%, respectively. The compounds were characterized via physical and spectroscopic techniques, namely elemental analysis (C, H, N), 1H and 13C Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy and melting point. The corrosion inhibiting property of the Schiff bases on mild steel in 1 M HCl solution was investigated by the weight loss (WL) measurements, electrochemical impedance spectroscopy (EIS) and linear polarization resistance (LPR). The concentrations of the Schiff bases were varied from 1 x 10-3 M to 1 x 10-5 M. The inhibition efficiencies obtained from all the methods employed were in good agreement where the percentage of inhibition efficiencies increased with concentration. OPI showed better inhibition efficiency than CPI with 91% highest inhibition efficiency at 1 x 10-3 M additive concentration. This is likely to be caused by the resonance donating effect due to the presence of the hydroxyl group. The adsorption behaviour obeyed Langmuir isotherm for monolayer formation.