Development and Validation of a Method for Quantification of Favipiravir as COVID-19 Management in Spiked Human Plasma

In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1–60.0 µg/mL with regression coefficient (r²) = 0.9976. However, with acceptable r², the calibration data’s heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday’s % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at −20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.     

Novel Synthesis of Some Phthalazinone Derivatives

Dimethyl homophthalate condensed with isatin to give the unexpected five membered lactone 3 rather than the half ester 1 and the δ‐lactone 2 . Treatment of compound 3 with excess hydrazine hydrate afforded phthalazinone carbohydrazide 4 which represents a novel method for the synthesis of phthalazinone derivatives. The carbohydrazide 4 upon treatment with carbon disulphide afforded 1,3,4‐oxadiazole derivative 5 , which reacted with ethylchloroacetate to give the S‐alkylated product 6 . The structure of compound 3 compared with 2 was discussed using hyperchem professional (7) AM₁ calculations, X‐ray single crystal structure and complete spectral data.     

Influence of the deposition method, temperature and deposition time on the corrosion inhibition of lead dodecanoate coatings deposited on lead surfaces

Electrochemical impedance measurements have been used to investigate the influence of the deposition method, including time and temperature, upon the corrosion inhibition characteristics of lead dodecanoate coatings on lead electrodes. The results were analysed using multivariate statistics and show that, in general, these easily prepared coatings are very protective against corrosion. The temperature proves to be an important parameter for the quality and the corrosion inhibition efficiency of the coating. A comparison between two different electrochemically assisted deposition methods, immersion using a reduction pretreatment and cyclic voltammetry, does not show significant differences. Using the immersion technique at room temperature, the deposition time was tested as the third influencing parameter for the corrosion inhibition efficiency of the deposited lead dodecanoate coatings. A longer deposition time of the lead into the sodium dodecanoate solution provides a layer with a somewhat higher corrosion resistance.     

Chemoenzymatic Late-Stage Modifications Enable Downstream Click-Mediated Fluorescent Tagging of Peptides

Aromatic prenyltransferases from cyanobactin biosynthetic pathways catalyse the chemoselective and regioselective intramolecular transfer of prenyl/geranyl groups from isoprene donors to an electron-rich position in these macrocyclic and linear peptides. These enzymes often demonstrate relaxed substrate specificity and are considered useful biocatalysts for structural diversification of peptides. Herein, we assess the isoprene donor specificity of the N1-tryptophan prenyltransferase AcyF from the anacyclamide A8P pathway using a library of 22 synthetic alkyl pyrophosphate analogues, of which many display reactive groups that are amenable to additional functionalization. We further used AcyF to introduce a reactive moiety into a tryptophan-containing cyclic peptide and subsequently used click chemistry to fluorescently label the enzymatically modified peptide. This chemoenzymatic strategy allows late-stage modification of peptides and is useful for many applications.     

Electrochemical deposition of dodecanoate on lead in view of an environmentally safe corrosion inhibition

Non-toxic linear sodium monocarboxylates can be successfully used as inhibitors for the corrosion of many metals. The adsorption of these molecules onto a metal is usually achieved by immersing the metal in the carboxylate solution for a few hours. This paper describes the strength of cyclic voltammetry in forming a sodium dodecanoate coating on a lead electrode. We show that this approach is much less time-consuming compared with the immersion method and enables one to control and to characterize the layer formed by following the potential and current during the process. Additional ATR-IR and X-ray diffraction spectroscopic analyses were performed to qualitatively characterize the newly formed coating.     

Synthesis and antitumor activity of new 1,2,4‐triazine and [1,2,4]triazolo[4,3‐b][1,2,4]triazine derivatives and their thioglycoside and acyclic C‐nucleoside analogs

New 1,2,4‐triazine and their derived 1,2,4‐triazolo[3,4‐b][1,2,4]triazine derivatives were synthesized starting from 5,6‐diphenyl‐1,2,4‐triazine‐3‐thiol. Furthermore, the corresponding 1,2,4‐triazolo[3,4‐b][1,2,4]‐triazine thioglycosides and acyclic C‐nucleoside analogs were synthesized. The newly synthesized compounds were evaluated for their antitumor activity and some of them showed high inhibition activities. J. Heterocyclic Chem., 2011.     

The Catalytic Mechanism of the Marine‐Derived Macrocyclase PatGmac

Cyclic peptides are a class of compounds with high therapeutic potential, possessing bioactivities including antitumor and antiviral (including anti‐HIV). Despite their desirability, efficient design and production of these compounds has not been achieved to date. The catalytic mechanism of patellamide macrocyclization by the PatG macrocyclase domain has been computationally investigated by using quantum mechanics/molecular mechanics methodology, specifically ONIOM(M06/6‐311++G(2d,2p):ff94//B3LYP/6‐31G(d):ff94). The mechanism proposed herein begins with a proton transfer from Ser783 to His 618 and from the latter to Asp548. Nucleophilic attack of Ser783 on the substrate leads to the formation of an acyl–enzyme covalent complex. The leaving group Ala‐Tyr‐Asp‐Gly (AYDG) of the substrate is protonated by the substrate's N terminus, leading to the breakage of the P1?P1′ bond. Finally, the substrate's N terminus attacks the P1 residue, decomposing the acyl–enzyme complex forming the macrocycle. The formation and decomposition of the acyl–enzyme complex have the highest activation free energies (21.1 kcal mol^?1 and 19.8 kcal mol^?1 respectively), typical of serine proteases. Understanding the mechanism behind the macrocyclization of patellamides will be important to the application of the enzymes in the pharmaceutical and biotechnological industries.     

Electrochemical strategies for the detection of forensic drugs

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Synthesis and Antimicrobial Activity of New 2,5‐Disubstituted 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles and Their Sugar Derivatives

A series of new 2,5‐disubstituted‐1,3,4‐oxadiazole and 1,2,4‐triazole derivatives were synthesized by heterocyclization of acid hydrazide 1 and thiosemicarbazide derivative 2 . Furthermore, the acyclic C‐nucleoside analogs were prepared by cyclization of their corresponding sugar hydrazones by reaction with acetic anhydride. The antimicrobial activity of the prepared compounds was evaluated and some of the synthesized compounds revealed good activities against fungi.