Cobalt-mediated approach for the synthesis of terpene-based hybrids

[structure: see text] Dicobalt-beta-pinene hybrids of types I and II have been prepared using a Nicholas reaction between propargyl derivatives, obtained from commercial (1R)-(-)-myrtenal, and different aromatic nucleophiles. The method is suitable for the preparation of densely functionalized bio-organometallic natural product-based hybrids, as demonstrated by the preparation of a beta-pinene-neoclerodane hybrid.     

A study on synthesis and antimicrobial activity of 4-acyl-pyrazoles

4-Acyl-pyrazole-3-carboxylic acids (1) were synthesized via the reaction of 4-acyl-2,3-furandiones (F) with hydrazone (1-benzylidene-2-(2,5-dimethyl-phenyl)-hydrazine) by heating under solid phase and their acid chlorides (2) were obtained. Then these derivatives were easily converted into the corresponding derivatives such as ester, amide, ureide, pyrazolo-pyridazine, etc. Totally 62 new compounds were synthesized. The structures of these new synthesized compounds were determined by spectroscopic methods and the in vitro antibacterial activity of newly synthesized compounds were carried out against some gram-positive and gram-negative bacteria by well diffusion method (zone inhibition). Our results have showed that these new synthesized compounds have much potent of antibacterial activity owing to containing of pyrazole and/or pyridazine, chromone, oxazine, furane, and pyrrole rings. Some of the new pyrazole derivatives exhibited higher activities than reference drugs against the representative bacteria.     

Hydroxypyridinones as “privileged” chelating structures for the design of medicinal drugs

Hydroxypyridinones (HPs) are a family of N-heterocyclic core chelators which, based on their specific metal-coordination, easy manipulation/derivatization and biocompatibility, have been an attractive target for the development of new pharmaceutical drugs with manifold uses. Herein we describe the most recent advances reported in the literature on HPs, with a special focus on the metal chelating properties of the 3-hydroxy-4-pyridinone (3,4-HP) derivatives, and the different approaches used to functionalize these chelators to improve their biological properties, namely in terms of bioavailability and specific bio-targeting abilities. Representative examples of HPs are included, mostly for applications as chelating drugs for sequestration or passivation of metal overload or deregulated biometals, but also as metallodrugs for potential diagnostic/therapeutic purposes. These examples are discussed in terms of the chelating properties and structure–activity relationships.     

Design,synthesis and antimicrobial evaluation of thioglycosides of a novel class of 2-mercaptonicotinonitriles

A new class of thioglycosides comprising a diazenyl pyridine moiety was assembled from the regioselective reaction of the acetylated α-glycopyranosyl bromide with hitherto unreported 2-mercaptonicotinonitriles. Moreover, the deacetylation of S-glycoside derivatives utilizing of methanolic ammonia solution afforded the free hydroxy thioglycosides in quantitative yields. The identity of the newly obtained derivatives has been achieved via spectroscopic and elemental analyses. All of the newly synthesized derivatives exhibited significant antimicrobial activity towards certain selected microorganisms (bacteria and fungi). Generally, S-glycoside derivatives demonstrated outstanding antibacterial and antifungal activities. Amongst them, the acetylated derivatives showed the most distinguished antifungal and antibacterial activities with a promising minimum inhibitory concentration (MIC) values in comparison with the approved drugs; Amphotericin B and Cefotaxime.     

Function‐Oriented Synthesis: How to Design Simplified Analogues of Antibacterial Nucleoside Natural Products?

It is important to pursue function‐oriented synthesis (FOS), a strategy for the design of less structurally complex targets with comparable or superior activity that can be made in a practical manner, because compared to synthetic drugs, many biologically relevant natural products possess large and complex chemical structures that may restrict chemical modifications in a structure–activity relationship study. In this account, we describe recent efforts to simplify complex nucleoside natural products including caprazamycins. Considering the structure–activity relationship study with several truncated analogues, three types of simplified derivatives, namely, oxazolidine, isoxazolidine, and lactam‐fused isoxazolidine‐containing uridine derivatives, were designed and efficiently synthesized. These simplified derivatives have exhibited promising antibacterial activities. A significant feature of our studies is the rational and drastic simplification of the molecular architecture of caprazamycins. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug‐resistant bacteria.     

Biological Activity of Newly Synthesized Benzimidazole and Benzothizole 2,5-Disubstituted Furane Derivatives

Newly designed and synthesized cyano, amidino and acrylonitrile 2,5-disubstituted furane derivatives with either benzimidazole/benzothiazole nuclei have been evaluated for antitumor and antimicrobial activity. For potential antitumor activity, the compounds were tested in 2D and 3D cell culture methods on three human lung cancer cell lines, A549, HCC827 and NCI-H358, with MTS cytotoxicity and BrdU proliferation assays in vitro. Compounds 5, 6, 8, 9 and 15 have been proven to be compounds with potential antitumor activity with high potential to stop the proliferation of cells. In general, benzothiazole derivatives were more active in comparison to benzimidazole derivatives. Antimicrobial activity was evaluated with Broth microdilution testing (according to CLSI (Clinical Laboratory Standards Institute) guidelines) on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Additionally, Saccharomyces cerevisiae was included in testing as a eukaryotic model organism. Compounds 5, 6, 8, 9 and 15 showed the most promising antibacterial activity. In general, the compounds showed antitumor activity, higher in 2D assays in comparison with 3D assays, on all three cell lines in both assays. In natural conditions, compounds with such an activity profile (less toxic but still effective against tumor growth) could be promising new antitumor drugs. Some of the tested compounds showed antimicrobial activity. In contrast to ctDNA, the presence of nitro group or chlorine in selected furane-benzothiazole structures did not influence the binding mode with AT-DNA. All compounds dominantly bound inside the minor groove of AT-DNA either in form of monomers or dimer and higher-order aggregates.     

Synthesis and antibacterial activity of Schiff bases of 5-substituted isatins

Based on the existing reports on the bioactive isatin derivatives, a number of Schiff bases were synthesized by reacting 5-substituted isatins with bioactive amines/hydrazides and their structures were confirmed using spectroscopic methods such as NMR, IR and mass spectrometry. Furthermore, Nbenzylation of isatin followed by the Schiff base formation furnished a new series of compounds(11a–13c) which allowed the analysis of the effect of isatin N-substitution on the bioactivity of the resulting compounds. The antibacterial activity of the synthesized derivatives was evaluated using a microtiter plate method on a series of gram positive and gram negative bacterial strains. Compounds 2d, 3b, 5c and 6a were among the most potent derivatives against Pseudomonas aeruginosa(MIC = 6.25 μg/m L).Analysis of the structure–activity relationship showed that the incorporation of(thio)urea-based Schiff bases lead to more potent derivatives with a broader spectrum of antibacterial activity. In addition,highly lipophilic compounds such as 11a–12c did not show any measurable antibacterial activity, which implies that an optimal lipophilicity might be an important requirement for the antibacterial activity of the studied isatins. Finally, the finding that hydantoin derivatives of N-benzylisatins(13a–13c) still exhibit some antibacterial activity prompted us to consider exploring the bioactivity of more diverse derivatives of isatin-aminohydantoin Schiff bases(compounds 1a–1d) in our future studies.     

Antibacterial potential of citral derivatives

Nine conjugated acid derivatives from monoterpene citral have been synthesized using ester, amide condensations, Wittig, Knoevenagel, Baylis-Hillman reactions and their antimicrobial activities were evaluated through disc diffusion and serial dilution methods. Several derivatives displayed interesting antimicrobial activity. Particularly, the Baylis-Hillman adducts 8-10 were found to have more potent antibacterial and antifungal activities than standard drugs namely chloramphenicol and nystatin respectively.     

二氢吲哚-2,3-二酮衍生物抑菌活性研究进展

二氢吲哚-2,3-二酮是一种结构简单且应用广泛的药物小分子,其衍生物的合成、结构和药理活性等备受关注。已有报道表明二氢吲哚-2,3-二酮具有抗菌、抗衰老、降血脂、抗癫痫、抗病毒等多种生物活性。本文主要围绕抑菌生物活性,对国内外关于二氢吲哚-2,3-二酮类化合物的构效关系进行分析总结,为后期该类新型抗菌化合物的设计合成提供参考。     

Novel Synthetic Routes to Prepare Biologically Active Quinoxalines and Their Derivatives: A Synthetic Review for the Last Two Decades

Quinoxalines, a class of N-heterocyclic compounds, are important biological agents, and a significant amount of research activity has been directed towards this class. They have several prominent pharmacological effects like antifungal, antibacterial, antiviral, and antimicrobial. Quinoxaline derivatives have diverse therapeutic uses and have become the crucial component in drugs used to treat cancerous cells, AIDS, plant viruses, schizophrenia, certifying them a great future in medicinal chemistry. Due to the current pandemic situation caused by SARS-COVID 19, it has become essential to synthesize drugs to combat deadly pathogens (bacteria, fungi, viruses) for now and near future. Since quinoxalines is an essential moiety to treat infectious diseases, numerous synthetic routes have been developed by researchers, with a prime focus on green chemistry and cost-effective methods. This review paper highlights the various synthetic routes to prepare quinoxaline and its derivatives, covering the literature for the last two decades. A total of 31 schemes have been explained using the green chemistry approach, cost-effective methods, and quinoxaline derivatives’ therapeutic uses.     

Targeting SARS-CoV-2 Polymerase with New Nucleoside Analogues

Despite the fact that COVID-19 vaccines are already available on the market, there have not been any effective FDA-approved drugs to treat this disease. There are several already known drugs that through drug repositioning have shown an inhibitory activity against SARS-CoV-2 RNA-dependent RNA polymerase. These drugs are included in the family of nucleoside analogues. In our efforts, we synthesized a group of new nucleoside analogues, which are modified at the sugar moiety that is replaced by a quinazoline entity. Different nucleobase derivatives are used in order to increase the inhibition. Five new nucleoside analogues were evaluated with in vitro assays for targeting polymerase of SARS-CoV-2.     

Design,synthesis and in vitro antibacterial activities of methyl-4-((substituted phenyl)[6H-indolo(2,3-b)quinoxalin-6-yl]methyl-amino)benzoate derivatives

A series of new methyl-4-((substituted phenyl)[6H-indolo(2,3-b)quinoxalin-6yl]methylamino)benzoate derivatives have been synthesized and assayed for their antibacterial activity on 9 different bacterial strains.Among the screened compounds 2e-2g exhibited potent inhibitory activity compared to standard drug employed,worth further investigation.     

Synthesis of some new 2-substituted-4-sulfamoylphenylazo-thiophene and/or thiazole derivatives as antibacterial agents

Benzoylacetone has been reacted with phenyl isothiocyanate to afford two different thiocarbamoyl derivatives (α-phenylthiocarbamoyl benzoylacetone and benzoyl thioacetanilide) depending upon the base used to perform the reaction. Several new 2-substituted-4-sulfamoylphenylazo-thiophene and/or thiazole derivatives were synthesized by heterocyclization of the thiocarbamoyl derivatives with various halogenated reagents. The synthesized compounds were screened for their antibacterial activities; they showed accepted activities with respect to the control drugs.     

Microwave Assisted Synthesis of N-Aryl-N'-[5-(4- Chlorophenyl)-2-Furoyl]-Thioureas And Ureas

Substituted thioureas have attracted much attention due to their herbicidal1, antibacterial2, anti-HIV3 and plant-growth regulating4 activity. Meanwhile substituted ureas are not only used as medicines and agrochemicals because of their antiinflammatory5, analgesic5 and insectcidal6 activity, but also used as intermediates for the synthesis of many important heterocyclic compounds. In addition, 5-aryl-2-furoic acid derivatives have been used as antibacterial agent7, local anesthesia8, analgesic9 and plant-growth regulator10. Therefore, with the objective of obtaining new biologically active compounds, it is necessary to investigate the convenient and efficient method to prepare new compounds bearing 5-aryl-2-furoyl and thiourea or 5-aryl-2-furoyl and urea moieties.     

Synthesis and in vitro Antimicrobial Activity of New Ethyl 2-(Ethoxyphosphono)-1-cyano-2-(substituted tetrazolo-[1,5-a]quinolin-4-yl)ethanoate Derivatives

A series of new ethyl 2‐(ethoxyphosphono)‐1‐cyano‐2‐(substituted tetrazolo[1,5‐a]quinolin‐4‐yl)ethanoate derivatives have been synthesized for the first time of tetrazolo[1,5‐a]quinoline derivatives. Elemental analysis, IR, ¹H NMR, ¹³C NMR, ³¹P NMR and mass spectral data elucidated the structures of the all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Gram‐positive Bacillus subtilis, Gram‐negative Escherichia coli and two fungi Candida albicans and Aspergillus niger in comparison with standard drugs. Significantly microbiological behavior of these newly synthesized derivatives possesses significant antibacterial and antifungal activity.     

A New Pyrimidine Schiff Base with Selective Activities against Enterococcus faecalis and Gastric Adenocarcinoma

Enterococcus faecalis is known as a significant nosocomial pathogen due to its natural resistance to many antibacterial drugs. Moreover, it was found that E. faecalis infection causes inflammation, production of reactive oxygen species, and DNA damage to human gastric cancer cells, which can induce cancer. In this study, we synthesized and tested the biological activity of a new Schiff base, 5-[(4-ethoxyphenyl)imino]methyl-N-(4-fluorophenyl)-6-methyl-2-phenylpyrimidin-4-amine (3), and compared its properties with an analogous amine (2). In the biological investigation, 3 was found to have antibacterial activity against E. faecalis 29212 and far better anticancer properties, especially against gastric adenocarcinoma (human Caucasian gastric adenocarcinoma), than 2. In addition, both derivatives were non-toxic to normal cells. It is worth mentioning that 3 could potentially inhibit cancer cell growth by inducing cell apoptosis. The results suggest that the presence of the –C=N– bond in the molecule of 3 increases its activity, indicating that 5-iminomethylpyrimidine could be a potent core for further drug discovery research.     

Synthesis,spectral studies,thermal behavior,and antibacterial activity of Ni(Ⅱ),Cu(Ⅱ),and Zn(Ⅱ) complexes with an ONO tridentate Schiff base

Three new transition metal complexes have been synthesized with a Schiff base,3-(2-hydroxy-5-chlorophenylimino)-l,3- diphenylpropen-1-one.In all complexes Schiff base is completely deprotonated and coordinated to metal as tridentate ligand via phenolic and enolic oxygens and imine nitrogen.Thermal decomposition of the complexes has been studied by thermogravimetry. The in vitro antibacterial activity of Schiff bases and their complexes has been evaluated and compared with the standard drugs.