Malonic Acid-Type Fullerene Derivatives Strongly Inhibit The SARS-Cov-2 Main Protease

COVID-19 is a disease that is causing a global pandemic. There is an urgent need to develop new drugs to treat it. In this study, we evaluated the inhibitory activities of a series of fullerene derivatives against the main protease of SARS-CoV-2, the virus that causes COVID-19. As a result, it was found that the malonic acid-type fullerene derivatives showed strong inhibitory activities.

Design, Synthesis and Spectroscopic Characterizations of Medicinal Hydrazide Derivatives and Metal Complexes of Malonic Ester

Background: A new series of malonic acid-based hydrazide derivatives (BPMPDH, 2HPMPDH, 3HPMPDH, 4HPMPDH, DMPDH) are successfully synthesized by the reaction of malonic ester hydrazide with various substituted aldehydes like salicylaldehyde, benzaldehyde, 4-hydroxy benzaldehyde, 3-hydroxy benzaldehyde and formaldehyde) Methods: metal complexes of prepared hydrazide derivatives were prepared using metals like Cu+2, Zn+2 and Ni+2 via a mild, efficient and convenient method. Newly synthesized compounds were characterized by IR, NMR (1H & 13C), UV/VIS and mass spectrometry. The presence of –C=N- peak at 1600-1700 cm-1 with the absence of NH2 peak at 3500 cm-1 in FTIR spectra. In 1HNMR peak at, 11.00-13.00 ppm for –OH protons and 7.00-9.50 ppm for –NH verified the synthesis of new hydrazide derivatives. The presence of a C-OH sharp peak at 180-190 ppm, a C=O peak at 160-170 ppm and a C=N peak at 140-150 ppm confirmed synthesis. In mass spectra, the molecular ion peaks at 308 m/z, 340 m/z and 156 m/z confirmed synthesis. Synthesized compounds have also been analyzed for their antioxidant, antibacterial, antifungal, chymotrypsin and tyrosinase inhibition activities Result and Conclusion: The results revealed that the 2HPMPDH, 3HPMPDH, 4HPMPDH and their Cu+2 and Zn+2 metal complexes showed more successful inhibition against standard drugs, based on structure activity relationship.

Heterogenous Clinical Landscape in a Consanguineous Malonic Aciduria Family

Malonic aciduria is an extremely rare inborn error of metabolism due to malonyl-CoA decarboxylase deficiency. This enzyme is encoded by the MLYCD (Malonyl-CoA Decarboxylase) gene, and the disease has an autosomal recessive inheritance. Malonic aciduria is characterized by systemic clinical involvement, including neurologic and digestive symptoms, metabolic acidosis, hypoglycemia, failure to thrive, seizures, developmental delay, and cardiomyopathy. We describe here two index cases belonging to the same family that, despite an identical genotype, present very different clinical pictures. The first case is a boy with neonatal metabolic symptoms, abnormal brain MRI, and dilated cardiomyopathy. The second case, the cousin of the first patient in a consanguineous family, showed later symptoms, mainly with developmental delay. Both patients showed high levels of malonylcarnitine on acylcarnitine profiles and malonic acid on urinary organic acid chromatographies. The same homozygous pathogenic variant was identified, c.346C > T; p. (Gln116*). We also provide a comprehensive literature review of reported cases. A review of the literature yielded 52 cases described since 1984. The most common signs were developmental delay and cardiomyopathy. Increased levels of malonic acid and malonylcarnitine were constant. Presentations ranged from neonatal death to patients surviving past adolescence. These two cases and reported patients in the literature highlight the inter- and intrafamilial variability of malonic aciduria.

CPExtract, a Software for the Automated Tracer-Based Pathway Specific Screening of Secondary Metabolites in LC-HRMS Data

The use of stable isotopically labeled tracers is a long-proven way of specifically detecting and tracking derived metabolites through a metabolic network of interest. While recently developed stable isotope assisted methods and associated, supporting data analysis tools have greatly improved untargeted metabolomics approaches, no software tool is currently available that allows to automatically search LC-HRMS chromatograms for completely free user-definable isotopolog patterns expected for the metabolism of labeled tracer substances. Here we present Custom Pattern Extract (CPExtract), a versatile software tool that allows for the first time the high-throughput search for user-defined isotopolog patterns in LC-HRMS data. The patterns can be specified via a set of rules including the presence or absence of certain isotopologs, their relative intensity ratios as well as chromatographic co-elution. Each isotopolog pattern satisfying the respective rules is verified on a MS-scan level and also in the chromatographic domain. The CPExtract algorithm allows the use of both labeled tracer compounds in non-labeled biological samples as well as a reversed tracer approach, employing non-labeled tracer compounds along with globally labeled biological samples. In a proof of concept study we searched for metabolites specifically arising from the malonate pathway of the filamentous fungi Fusarium graminearum and Trichoderma reesei. 1,2,3- 13 C 3 -malonic acid diethyl ester and native malonic acid monomethyl ester were used as tracers. We were able to reliably detect expected fatty acids and known polyketides. In addition, up to 189 and 270 further, unknown metabolites presumably including novel polyketides were detected in the F. graminearum and T. reesei culture samples respectively, all of which exhibited the user-predicted isotopolog patterns originating from the malonate tracer incorporation. The software can be used for every conceivable tracer approach. Furthermore, the rule sets can be easily adapted or extended if necessary. CPExtract is available free of charge for non-commercial use at https://metabolomics-ifa.boku.ac.at/CPExtract.

Molecular Dynamics Study on the Leaching of Zinc-Bearing Dust Sludge by Choline Chloride-Malonic Acid

Molecular dynamics of the interaction between four metal oxides (ZnO, Fe2O3, Al2O3, and CaO) present in zinc-bearing dust sludge and choline chloride (ChCl)-malonic acid (MA)(1:2) was studied in this work using Materials Studio software. The interaction mechanism was revealed by analyzing the interaction energy and radial distribution function from the perspective of quantum mechanics, and the simulation results were verified by single factor leaching experiments. The calculation results show that the complete cleavage surface of the four metal oxides is the (001) surface, and ChCl-2MA forms a stable structure with multiple intermolecular hydrogen bonds centered on the chlorine atom. The dynamic simulation of the interaction model shows that strength of interaction between ChCl-2MA and the four metal oxides follows the order: ZnO > Fe2O3 > Al2O3 > CaO. ChCl-2MA mainly interacts with ZnO by chemical adsorption, while ChCl-2MA mainly interacts with Fe2O3, Al2O3, and CaO by physical adsorption. The radial distribution function shows that Cl in ChCl-2MA and C=O in MA form chemical bonds with Zn in ZnO, and the choline cation (Ch+) forms C-H···O with ZnO. Among these bonds, the Cl-Zn bond energy is stronger. During the interaction between ChCl-2MA and Fe2O3 and Al2O3, O-H···O and C-H···O are formed and interact with CaO by van der Waals force. Single factor leaching experiments show that, under the same leaching conditions, the leaching rate of ZnO by ChCl-2MA is greater than 90%, while the leaching rate of Fe2O3, Al2O3, and CaO is about 10%. These results indicate good selectivity of ChCl-2MA for ZnO in the zinc-bearing dust sludge. The above conclusions have important theoretical significance and provide an in-depth understanding of the leaching mechanisms of zinc-bearing dust sludge in deep eutectic solvents.