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1-Adamantylhydrazine can be a versatile intermediate for many biologically active compounds as adamantyl possesses a wide spectrum of medicinal properties. Described here is a detailed one-pot synthesis of 1-adamantylhydrazine, carried out on a milligram to gram scale, that steadily delivers a highly stable product used to carry out the synthesis of 1-(adamantan-1-yl)-1 H -pyrazol-3-amine for bacterial studies. The reaction employs inexpensive, catalyst free, readily available starting materials. In the synthesis of 1-(adamantan-1-yl)-1 H -pyrazol-3-amine, the use of a continuous extraction method allows for complete extraction of the target product into the organic layer and increases the overall percentage yield. [ABSTRACT FROM AUTHOR]

During the red blood cell phase of their life cycle, malaria parasites digest their host's haemoglobin, with concomitant release of potentially toxic iron(iii) protoporphyrin IX (FePPIX). The parasites’ strategy for detoxification of FePPIX involves its crystallization to haemozoin, such that the build-up of free haem in solution is avoided. Antimalarial drugs of both historical importance and current clinical use are known to be capable of disrupting the growth of crystals of β-haematin, which is the synthetic equivalent of haemozoin. Hence, the disruption of haemozoin crystal growth is implicated as a possible mode of action of such drugs. However, the details of β-haematin crystal poisoning at the molecular level have yet to be fully elucidated. In this study, we have used a combination of density functional theory (DFT) and molecular modelling to examine the possible modes of action of ten different antimalarial drugs, including quinine-type aliphatic alcohols, amodiaquine-type phenols, and chloroquine-type aliphatic diamines. The DFT calculations indicate that each of the drugs can form at least one molecular complex with FePPIX. These complexes have 1 : 1 or 2 : 1 FePPIX : drug stoichiometries and all of them incorporate Fe–O bonds, formed either by direct coordination of a zwitterionic form of the drug, or by deprotonation of water. Most of the drugs can form more than one such complex. We have used the DFT model structures to explore the possible formation of a monolayer of each drug–haem complex on four of the β-haematin crystal faces. In all cases, the drug complexes can form a monolayer on the fast-growing {001} and {011} faces, but not on the slower growing {010} and {100} faces. Additional modelling of the chloroquine and quinidine complexes shows that individual molecules of these species can also obstruct the growth of new layers on other crystal faces. The implications of these observations for antimalarial drug development are discussed. [ABSTRACT FROM AUTHOR]

This study explored, for the first time, the antioxidant (total antioxidant content, reducing power, ferric ion reducing antioxidant power, hydroxyl radical scavenging, ferrous ion-chelating assays), anti-tyrosinase, anti-inflammatory properties, and hepatoprotective effect in HepG2 cell lines of Ochna integerrima (Loureiro) Merrill flowers and seeds. All extracts except n -hexane exhibited significant antioxidant activity, with high levels of tannin and proanthocyanidins. Luteolin ( 1 ), 6- γ , γ -dimethylallylkaempferol7- O - β -d-glucopyranoside ( 2 ), 6- γ , γ -dimethylallylquercetin7- O - β -d-glucopyranoside ( 3 ), and 6- γ , γ -dimethylallyldihydrokaempferol 7- O - β -d-glucopyranoside ( 4 ) were isolated using semi-preparative HPLC. Compounds 1 - 3 demonstrated good anti-tyrosinase activity. The most active hepatoprotective extracts were found to be aqueous extracts. The flower extracts exhibited greater anti-inflammatory properties by the decrease of NO in RAW 264.7 cells and bovine serum albumin protein. Among them, the n -hexane and EtOAc extracts from flowers displayed promising anti-inflammatory activity. This was predicted by in silico analysis of 1 - 4 . In summary, O. integerrima appears to be a promising natural source for antioxidant, anti-tyrosinase, and anti-inflammatory applications.

A novel series of copper-activatable drugs intended for use against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) were synthesized, characterized, and tested against the MSSA strain Newman and the MRSA Lac strain (a USA300 strain), respectively. These drugs feature an NNSN structural motif, which enables the binding of copper. In the absence of copper, no activity against MSSA and MRSA at realistic drug concentrations was observed. Although none of the novel drug candidates exhibits a stereocenter, sub-micromolar activities against SA Newman and micromolar activities against SA Lac were observed in the presence, but not in the absence, of bioavailable copper. Copper influx is a component of cellular response to bacterial infections, which is often described as nutritional immunity., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)