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This review focuses on recent advancements in the efficacy of gold catalysts for the cycloisomerisation of ynamides, diynes, and 1,n-enynes to build complex molecules, with critical insight into their mechanism and reaction scope.

The antioxidant activity in tea is largely driven by its polyphenolic content, however, the antioxidant reaction mechanism and the compounds involved are not well characterized. Therefore, in this study, we performed in-depth profiling of the antioxidant reaction mechanism of Green Tea (GT), Black Tea (BT), and their polyphenolic fractions with free radical using state-of-the-art analytical techniques. The polyphenol enriched fractions from GT and BT were isolated using column chromatography. Catechins were isolated and characterized by diverse spectroscopic techniques. Samples were screened for their antioxidant activity by HPTLC and further evaluated using a spectrophotometer. The free radical reactions with GT, BT, enriched fractions viz, GT Polyphenols (GTP), BT Polyphenols (BTP), and isolated catechins were studied using the (13)C NMR technique. The highest polyphenol content was found in GTP (795.4 ± 0.012 mg/g) whereas GT (321.0 ± 0.028 mg/g) showed maximum flavonoids content. Individual catechins isolated from GTP were EGCG, ECG, EGC, EC and C. Antioxidant activity followed the order EGCG > ECG > EGC > EC > GTP > C > BTP > GT > BT. In GT, the antioxidant reaction mechanism showed single electron and H-transfer in all catechins, which involved the transformation of the hydroxyl group to the carbonyl group. Whereas in BT theaflavins, conversion of the benzotropolone ring to the six-membered ring was observed. GRAPHIC ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05297-w.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer in the world and the most prevalent cancer of developing countries. Increased disease burden and a smaller number of approved targeted therapies are a growing concern worldwide. Isoindolinone motifs have been a central part of many pharmacological compounds, and their derivatives possess substantial anticancer potential. However, their anticancer potential against HNSCC has not been well investigated. In the current study, a series of 3-methyleneisoindolinones have been designed and synthesized and their late-stage intramolecular Heck cyclization was achieved to evaluate their anticancer potential against HNSCC cells. Additionally

A V2O5@TiO2 catalyzed green and efficient protocol for the hydroxylation of boronic acid into phenol has been developed utilizing environmentally benign oxidant hydrogen peroxide. A wide range of electron-donating and the electron-withdrawing group-containing (hetero)aryl boronic acids were transformed into their corresponding phenol. The methodology was also applied successfully to transform various natural and bioactive molecules like tocopherol, amino acids, cinchonidine, vasicinone, menthol, and pharmaceuticals such as ciprofloxacin, ibuprofen, and paracetamol. The other feature of the methodology includes gram scale synthetic applicability, recyclability, and short reaction time.

The development of green and sustainable processes to synthesize active pharmaceutical ingredients and key starting materials is a priority for the pharmaceutical industry. A green and sustainable protocol for the oxidative cleavage of olefins to produce pharmaceutically and biologically valuable carboxylic acids is achieved. The developed protocol involves 70% aq. TBHP as an oxidant over a heterogeneous vanadium catalyst system. Notably, the synthesis of industrially important azelaic acid from various renewable vegetable oils is accomplished. The catalyst could be recycled for up to 5 cycles without significant loss in yield and the protocol was successfully demonstrated at the gram-scale.

Conjugates between pharmaceuticals and small molecules enable access to a vast chemical space required for the discovery of new lead molecules with modified therapeutic potential. However, the dearth of specific chemical reactions that are capable of functionalizing drugs and bioactive natural products presents a formidable challenge for preparing their conjugates. Here, we report a support-free CuI-nanoparticle-catalyzed strategy for conjugating electron-deficient and electron-rich terminal alkynes with a ciprofloxacin methyl ester. Our conjugation technique exploits the late-stage functionalization of bioactive natural products such as tocopherol, vasicinone, amino acids, and pharmaceuticals such as aspirin and paracetamol to provide conjugates in excellent yields under mild and green conditions. This protocol also enabled the synthesis of (hetero)arene-ciprofloxacin 1,4-disubstituted 1,2,3-triazoles in good yields and high regioselectivities. These synthesized ciprofloxacin conjugates were evaluated in vitro for their antibacterial activity against a panel of relevant bacteria. A significant number of conjugates showed comparable activity against Gram-positive and Gram-negative bacteria. Moreover, some conjugates exhibited less toxicity than ciprofloxacin against two mammalian cell lines, suggesting the utility for the future investigation of these compounds for in vivo efficacy and pharmacokinetic studies.

In Indian cold storage industry, the two most important problems are higher energy consumption and storage losses beyond the permissible limit. In India, storage losses in potato cold store account for 3–10% of the stored product. Major losses are in the form of rotting, cold injury weight losses, and sprouting nutritive value degradation. In the present work, airflow velocity is measured in a modeled cold storage room with the help of ANSYS software. The data which is collected from ANSYS FLUENT 14.5 is the temperature records, and air velocity in monitor point and the distribution of temperature and air velocity in all nodes in model area. The velocity at top layer that is in front of evaporator is between 2.5 to 3 m/s and decreases drastically with distance from source. Airflow improves in the cold storages with the help of duct with slotted arrangement.

WHO has declared COVID-19 a pandemic, which has affected the whole world and has caused unprecedented social and economic disruption. Since the emergence of the disease, several druggable targets have been suggested including 3-chymotrypsin-like protease (3CL(pro)), spike, RNA-dependent RNA polymerase (RdRp), and the papain-like protease (PL(pro)) computational approach. From the beginning, viral replication has been the main focus for any antiviral drug development for viral diseases, including HCV, influenza virus, zika virus, norovirus, measles, dengue virus, and coronaviruses. This review lists the nucleoside, nucleotide, and non-nucleoside RdRp inhibitor analogues of various viral diseases that may be evaluated for drug development to treat COVID-19.

Across the globe, countries are being challenged by the SARS-CoV-2 (COVID-19) pandemic in ways they have never been before. The global outbreak of SARS-CoV-2 with an uncertain fatality rate has imposed extreme challenges on global health. The World Health Organization (WHO) has officially declared the outbreak of COVID-19 a pandemic, after the disease caused by the new coronavirus spread to more than 100 countries. To date, various therapeutic approaches have been proposed and are being implemented to combat this pandemic, but unfortunately, no sovereign remedy has been established yet. Protease enzymes are important targets to develop therapies for the treatment of infections caused by SARS coronaviruses. In this review, an overview is given on recent advances in the discovery of potent protease inhibitors targeting the SARS coronaviruses. Different classes of natural product inhibitors targeting protease enzymes of SARS coronaviruses have been studied in detail along with their structure-activity relationship analysis. This study emphasized important covalent and non-covalent small molecule inhibitors, which effectively inhibited chymotrypsin- like cysteine protease (3CLpro) and papain-like protease (PLpro) of two SARS coronaviruses, i.e., SARS-CoV-1 and SARS-CoV-2. Repurposing of drugs has also been outlined in this study to understand their roles as quick-to-be-identified therapy to combat these zoonotic coronaviruses.

Toxicity of sugar embedded macrocycles was evaluated for their toxicity against nymphs of aphid, Aphis craccivora Koch (Hemiptera: Aphididae) in the laboratory conditions. Most of the compounds sho...

The potential of 2-aminoquinazolin-4(3H)-one as an organocatalyst for the activation of aldehydes via noncovalent interaction for the synthesis of tertiary amines using formic acid as a reducing agent is reported for the first time. The developed protocol demonstrated a dilated substrate scope for aromatic and aliphatic amines with aromatic and aliphatic aldehydes. Furthermore, the current method was also fruitful for the derivatization of ciprofloxacin and its derivative in good to excellent yields.

A novel, mild and transition metal-free, 2-aminoquinazolin-4(3H)-one-assisted reduction of nitroarenes employing hydrazine hydrate as reducing agent and potassium carbonate as a base is reported. For the first time, the activation of hydrazine hydrate with an organocatalyst has been explored for reduction reactions. Also for the first time, 2-aminoquinazolin-4(3H)-one and its derivatives have been investigated as hydrogen bonding organocatalysts for the reduction of nitroarenes to anilines. Sensitive functional groups such as sulfonamide, carboxyl, amide and halides were well tolerated in this green methodology with scalability and high chemoselectivity.

The World Health Organization has categorized the Gram-negative superbugs, which are inherently impervious to many antibiotics, as critical priority pathogens due to the lack of effective treatments. The breach in our last-resort antibiotic (i.e., colistin) by extensively drug-resistant and pan-drug-resistant Enterobacteriaceae strains demands the immediate development of new therapies. In the present study, we report the discovery of tridecaptin M, a new addition to the family, and its potential against colistin-resistant Enterobacteriaceae in vitro and in vivo. Also, we performed mode-of-action studies using various fluorescent probes and studied the hemolytic activity and mammalian cytotoxicity in two cell lines. Tridecaptin M displayed strong antibacterial activity (MICs of 2 to 8 μg ml−1) against clinical strains of Klebsiella pneumoniae (which were resistant to colistin, carbapenems, third- and fourth-generation cephalosporins, fluoroquinolones, fosfomycin, and other antibiotics) and mcr-1-positive Escherichia coli strains. Unlike polymyxins, tridecaptin M did not permeabilize the outer membrane or cytoplasmic membrane. It blocked ATP synthesis in bacteria by dissipating the proton motive force. The compound exhibited negligible acquired resistance, low in vitro cytotoxicity and hemolytic activity, and no significant acute toxicity in mice. It also showed promising efficacy in a thigh infection model of colistin-resistant K. pneumoniae. Altogether, these results demonstrate the future prospects of this class of antibiotics to address the unmet medical need to circumvent colistin resistance in extensively drug-resistant Enterobacteriaceae infections. The work also emphasizes the importance of natural products in our shrunken drug discovery pipeline.

The World Health Organization has categorized the Gram-negative superbugs, which are inherently impervious to many antibiotics, as critical priority pathogens due to the lack of effective treatments. The breach in our last-resort antibiotic (i.e., colistin) by extensively drug-resistant and pan-drug-resistant Enterobacteriaceae strains demands the immediate development of new therapies., The World Health Organization has categorized the Gram-negative superbugs, which are inherently impervious to many antibiotics, as critical priority pathogens due to the lack of effective treatments. The breach in our last-resort antibiotic (i.e., colistin) by extensively drug-resistant and pan-drug-resistant Enterobacteriaceae strains demands the immediate development of new therapies. In the present study, we report the discovery of tridecaptin M, a new addition to the family, and its potential against colistin-resistant Enterobacteriaceae in vitro and in vivo. Also, we performed mode-of-action studies using various fluorescent probes and studied the hemolytic activity and mammalian cytotoxicity in two cell lines. Tridecaptin M displayed strong antibacterial activity (MICs of 2 to 8 μg ml−1) against clinical strains of Klebsiella pneumoniae (which were resistant to colistin, carbapenems, third- and fourth-generation cephalosporins, fluoroquinolones, fosfomycin, and other antibiotics) and mcr-1-positive Escherichia coli strains. Unlike polymyxins, tridecaptin M did not permeabilize the outer membrane or cytoplasmic membrane. It blocked ATP synthesis in bacteria by dissipating the proton motive force. The compound exhibited negligible acquired resistance, low in vitro cytotoxicity and hemolytic activity, and no significant acute toxicity in mice. It also showed promising efficacy in a thigh infection model of colistin-resistant K. pneumoniae. Altogether, these results demonstrate the future prospects of this class of antibiotics to address the unmet medical need to circumvent colistin resistance in extensively drug-resistant Enterobacteriaceae infections. The work also emphasizes the importance of natural products in our shrunken drug discovery pipeline.

A synthetic approach to skeletally diverse alkaloid-like compounds, involving two consecutive three-component reactions, was developed. First, reaction between a range of secondary amines, carbonyl compounds and triazines yielded cyclic imines. Crucially, the identity of the substituents in the amine and carbonyl compound components determined ― through a "folding" pathway - the alkaloid-like scaffold that was prepared. The cyclic imine products were substrates for a second reaction, most usually a Joullie―Ugi reaction with an isocyanide and a carboxylic acid. Thus, the final products were, in general, ultimately derived from five separate components, and wide and independent variation of the substitution of each scaffold was possible. The 43 products were based on 28 distinct graph-node level frameworks. The high skeletal diversity of the products stemmed both from the "folding" pathway used to define the scaffolds of the cyclic imines, and from cyclic substituents used in each of the components.

An efficient synthesis of spiroannulated dihydroisobenzofurans is achieved using easily accessible carbohydrate-derived furanyl propargyl ethers via an AuCl 3 promoted intramolecular Diels–Alder (IMDA) reaction. The scope of the spiroannulation protocol was demonstrated using a diverse range of pentofuranosyl, hexofuransoyl and hexopyranosyl derived substrates in order to synthesize spiroannulated dihydroisobenzofurans. The reaction is high yielding, moisture tolerant, fast and uses only a catalytic amount of AuCl 3 .

The stereoselective synthesis of spiroannulated cyclopentenones by the Pauson–Khand reactions on hexose and pentose derived enynes was achieved under carbon monoxide free conditions using a stoichiometric quantity of Co 2 (CO) 8 . The cobalt complex of the alkyne was cleaved using dimethoxyethane–acetonitrile at 85 °C to furnish spiroannulated cyclopentenones in 75–94% yields.

The vapor phase oxidation of 4-fluorotoluene has been carried out over vanadia-titania catalysts with moderate conversion and selectivity for 4-fluorobenzaldehyde. Two series of V 2 O 5 /TiO 2 catalysts with 1-10 mol% vanadia were prepared by sol-gel technique using vanadium and titanium peroxide as vanadia and titania precursors respectively and by impregnation technique using vanadium peroxide on anatase titania support. The samples were characterized by X-ray diffraction, NH 3 -TPD, FT-IR and BET surface area measurements. The XRD of the catalysts prepared by impregnation technique showed retention of the anatase titania whereas the catalysts prepared by sol-gel technique showed the formation of rutile titania with minor amount of anatase phase at lower vanadia content (1-3%), which completely transformed into anatase phase at higher vanadia loading. The samples prepared by sol-gel method showed higher acidity and surface area compared to the samples prepared by impregnation. Pyridine adsorption study by FT-IR revealed the presence of Lewis acidity at lower vanadia loading (1-3%) and presence of both Lewis as well as Bronsted acidity at higher vanadia loading. The catalytic activity for oxidation of 4-fluorotoluene increased with vanadia loading in the sol-gel catalysts. The catalysts prepared by impregnation technique were found to be less active. However the selectivity for 4-fluorobenzaldehyde decreased with increase in vanadia content. The influence of vanadia loading, reaction temperature and contact time on the catalytic activity for 4-fluorotoluene oxidation has been investigated. The structure of the catalyst and its catalytic activity has been correlated.

Cryptosporidium parvum is an important human pathogen and potential bioterrorism agent. This protozoan parasite cannot salvage guanine or guanosine and therefore relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for biosynthesis of guanine nucleotides and hence for survival. Because C. parvum IMPDH is highly divergent from the host counterpart, selective inhibitors could potentially be used to treat cryptosporidiosis with minimal effects on its mammalian host. A series of 1,2,3-triazole containing ether CpIMPDH inhibitors are described. A structure-activity relationship study revealed that a small alkyl group on the alpha-position of the ether was required, with the (R)-enantiomer significantly more active than the (S)-enantiomer. Electron-withdrawing groups in the 3- and/or 4-positions of the pendent phenyl ring were best, and conversion of the quinoline containing inhibitors to quinoline-N-oxides retained inhibitory activity both in the presence and absence of bovine serum albumin. The 1,2,3-triazole CpIMPDH inhibitors provide new tools for elucidating the role of IMPDH in C. parvum and may serve as potential therapeutics for treating cryptosporidiosis.

The stereoselective synthesis of spiroannulated cyclopentenones by the Pauson–Khand reactions on hexose and pentose derived enynes was achieved under carbon monoxide free conditions using a stoichiometric quantity of Co 2 (CO) 8 . The cobalt complex of the alkyne was cleaved using dimethoxyethane–acetonitrile at 85 °C to furnish spiroannulated cyclopentenones in 75–94% yields.

Fluorotoluenes have been nitrated regioselectively in the liquid phase under mild conditions using solid acid catalysts. Excellent yields were obtained with 70% nitric acid as nitrating agent. Nitration of 2-fluorotoluene at 90 °C showed 55% conversion with 90% selectivity for 2-fluoro-5-nitrotoluene whereas 3-fluorotoluene showed more than 79% conversion even at 60 °C with 67% selectivity for 3-fluoro-6-nitrotoluene and 30% selectivity for 3-fluoro-4-nitrotoluene. In the case of 4-fluorotoluene, side chain nitration was observed instead of ring nitration with 53% conversion and 59% selectivity for 4-fluoro-α-nitrotoluene. Among the different catalysts studied for fluorotoluene nitration, Fe/Mo/SiO2, MoO3/SiO2 and H-beta showed higher conversion and selectivity in all three isomers due to higher acidity. A recycling study of catalyst H-beta for nitration of 3-fluorotoluene showed no significant loss in conversion as well as selectivity even after 5 recycles indicating the high stability of the catalyst. Compared to the conventional process, fluorotoluene nitration over solid acid catalysts is a highly regioselective, clean and environmentally friendly process with a simpler work up procedure.