A Comprehensive Review of Andrographis paniculata (Burm. f.) Nees and Its Constituents as Potential Lead Compounds for COVID-19 Drug Discovery

The COVID-19 pandemic has intensively disrupted global health, economics, and well-being. Andrographis paniculata (Burm. f.) Nees has been used as a complementary treatment for COVID-19 in several Asian countries. This review aimed to summarize the information available regarding A. paniculata and its constituents, to provide critical points relating to its pharmacological properties, safety, and efficacy, revealing its potential to serve as a source of lead compounds for COVID-19 drug discovery. A. paniculata and its active compounds possess favorable antiviral, anti-inflammatory, immunomodulatory, and antipyretic activities that could be beneficial for COVID-19 treatment. Interestingly, recent in silico and in vitro studies have revealed that the active ingredients in A. paniculata showed promising activities against 3CLpro and its virus-specific target protein, human hACE2 protein; they also inhibit infectious virion production. Moreover, existing publications regarding randomized controlled trials demonstrated that the use of A. paniculata alone or in combination was superior to the placebo in reducing the severity of upper respiratory tract infection (URTI) manifestations, especially as part of early treatment, without serious side effects. Taken together, its chemical and biological properties, especially its antiviral activities against SARS-CoV-2, clinical trials on URTI, and the safety of A. paniculata, as discussed in this review, support the argument that A. paniculata is a promising natural source for drug discovery regarding COVID-19 post-infectious treatment, rather than prophylaxis.     

Salinosporamide natural products: Potent 20 S proteasome inhibitors as promising cancer chemotherapeutics

Proteasome inhibitors are rapidly evolving as potent treatment options in cancer therapy. One of the most promising drug candidates of this type is salinosporamide A from the bacterium Salinispora tropica. This marine natural product possesses a complex, densely functionalized γ‐lactam‐β‐lactone pharmacophore, which is responsible for its irreversible binding to its target, the β subunit of the 20S proteasome. Salinosporamide A entered phase I clinical trials for the treatment of multiple myeloma only three years after its discovery. The strong biological activity and the challenging structure of this compound have fueled intense academic and industrial research in recent years, which has led to the development of more than ten syntheses, the elucidation of its biosynthetic pathway, and the generation of promising structure–activity relationships and oncological data. Salinosporamide A thus serves as an intriguing example of the successful interplay of modern drug discovery and biomedical research, medicinal chemistry and pharmacology, natural product synthesis and analysis, as well as biosynthesis and bioengineering.     

Analysis of methylene blue and its metabolites in blood by capillary electrophoresis/electrospray ionization mass spectrometry

A method for the determination of methylene blue (MB) and its metabolites (azure A, azure B and azure C) in rat blood by CE-electrospray ionization mass spectrometry (CE-ESI-MS) was developed in this paper. Different analytical parameters were investigated in detail such as pH and concentration of separation buffer, and ESI-MS instrumental parameters. Under the optimum conditions, MB and its metabolites were separated and detected in 27.3 min. LODs (defined as S/N=3) of this method were 0.22, 0.25, 0.10 and 0.30 μg/mL for MB, azure A, azure B and azure C, respectively. To get a satisfactory extraction efficiency of MB and its metabolites in rat blood, different extraction solutions were studied. By using this method, MB and its metabolites (azure A, azure B and azure C) were successfully analyzed in rat blood samples.     

浊点萃取在痕量金属元素分析中的应用

浊点萃取(CPE)法是一种新兴的环保型液_液萃取技术，可以作为痕量金属元素的预富集方法。此文总结了CPE法在痕量金属元素分析中应用原理、方法及试验条件优化，概括了CPE作为预富集法在不同分析检测仪器中的应用，探讨了该技术方法的应用前景。     

哌嗪及其共生物的气相色谱分析研究

研究了哌嗪及其共生物的气相色谱分析方法。采用Chromsorb WAW（60～80目）为担体,以氢氧化钾作减尾剂,聚乙二醇（PEG 2万）作固定液,在长 1.5m的玻璃填充柱上哌嗪及其共生物得到良好的分离。除乙二胺外,其他相对误差均小于2％。并且计算了哌嗪及其共生物的得率和原料的转化率。     

Promoter Methylation of RASSF1A Gene in Egyptian Patients with Ovarian Cancer

Ovarian malignancy is diagnosed in nearly a fourth of a million women internationally every year. Methylation of RASSF1A tumor suppressor gene prompts its inactivation in diseases. In this study, the RASSF1A promoter methylation was detected by methylated-specific PCR and investigated serum RASSF1A protein level through enzyme-linked immunosorbant assay in 160 Egyptian patients with ovarian cancer and 160 healthy controls. The present work proved that there was a higher frequency of RASSF1A methylation and a decrease in its serum level in patients with ovarian cancer compared to controls as well as in the high-grade tumor patients compared to low grade ones and also in advanced ovarian tumor stage compared to early stages. Our study exhibited that RASSF1A promoter hypermethylation and its protein levels may be a reliable and sensitive tool for diagnosing and monitoring of ovarian malignancy patients.     

Fluorotris(trifluoromethylsulfonyl)methane: synthesis, characterization and reactivity

The hitherto elusive title compound was synthesized and characterized with the aim to study its potential as a carbon-based (“CF-type”) electrophilic fluorination reagent. A detailed discussion of its structure, properties and reactivity is based on experimental studies as well as on molecular modeling.     

Stability and Antiproliferative Activity of Malvidin-Based Non-Oxonium Derivative (Oxovitisin A) Compared with Precursor Anthocyanins and Pyranoanthocyanins

Oxovitisins are a unique group of anthocyanin derivatives with a non-oxonium nature and α-pyranone (lactone) D ring on the structure. In this study, oxovitisin A was synthesized through the micro-oxidative reaction of carboxypyranomalvidin-3-O-glucoside (vitisin A) with water, and its thermostability, pH, and SO₂ color stability were studied compared with its two precursors, malvidin-3-O-glucoside (Mv3glc) and vitisin A, as well as methylpyrano-malvidin-3-O-glucoside (Me-py). Results showed that oxovitisin A exhibited the highest stabilities, which were inseparably related to its noncharged structure and the additional carbonyl group on the D ring. Moreover, the antiproliferative capacity of oxovitisin A was comparatively evaluated against two human gastrointestinal cancer cell lines. Interestingly, oxovitisin A presented the strongest antiproliferative ability on MKN-28 (IC₅₀ = 538.42 ± 50.06 μM) and Caco-2 cells (IC₅₀ = 434.85 ± 11.87 μM) compared with two other pyranoanthocyanins. Therefore, we conclude that oxovitisin A as a highly stable anthocyanin derivative still exhibits a satisfactory antiproliferative ability.     

Apis mellifera syriaca Venom: Evaluation of Its Anticoagulant Effect,Proteolytic Activity,and Cytotoxicity along with Its Two Main Compounds—MEL and PLA2—On HeLa Cancer Cells

Bee venom (BV) is one of the most remarkable natural products that has been a subject of studies since ancient times. Recent studies have shown that Apis mellifera syriaca venom possesses antibacterial as well as cytotoxic effects on cancer cell lines. The venom contains a variety of bioactive molecules—mainly melittin (MEL) and phospholipase A2 (PLA2), as well as other compounds that are not well characterized. In this work, we continue the biological characterization of A. mellifera syriaca venom by testing its anticoagulant effect on human plasma using the prothrombin time (PT) test, as well as assessing its proteolytic activity. In addition, the cytotoxicity of the crude venom—and of its two main components, MEL and PLA2—was tested on HeLa cancer cell lines for the first time. The results obtained showed the capacity of A. mellifera syriaca venom to increase clotting time, thereby proving its anticoagulant effect. Moreover, the venom did not demonstrate a significant proteolytic activity unless administrated at concentrations ≥ 5 mg/mL. Finally, we showed that crude A. mellifera syriaca venom, along with MEL, exhibit a strong in vitro cytotoxic effect on HeLa cancer cell lines, even at low concentrations. In summary, our findings could serve as a basis for the development of new natural-based drug candidates in the therapeutic field.     

抗生育药山甘草的新三萜皂苷

从民间抗生育药山苷草Mussaenda pubesecus的总皂苷酸水解产物中, 分离得到MP-C、D、E和F四个化合物, 经UV、IR、NMR、MS解析和化学方法, 确定了它们的化学结构。MP-C为一种新型的含有酰胺键接γ-内酯环的三萜化合物, 一新近报道的Heinsiagenin A的结构一致。MP-D、E和F分别为MP-C的β-D吡喃葡萄糖苷、β-D-吡喃木糖苷和β-D吡喃葡萄糖(1→2)-β-D-吡喃木糖苷, 均为新化合物, 分别命名为MussaendosideA、B和C。     

DETERMINATION OF MOLECULAR AND CRYSTAL STRUCTURES OF A UNIQUE NEW TETRATERPENOID——METHYL SARTORTUOATE

A unique new tetracyclic tetraterpenoid has been isolated from the Chinese soft coral Sarcophyton tortuosum Tixier-Durivault and designated as methyl sartortuoate. Its chemical and crystal structures as well as its absolute configuration were determined by IR, UV, NMR and X-ray diffraction analysis. The authors have also suggested a possible route for its biogenesis.     

Chemistry of Lipid A: At the Heart of Innate Immunity

In many Gram‐negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll‐like receptor 4/myeloid differentiation factor 2 (TLR4/MD‐2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock. Since the bioactivity of lipid A is strongly influenced by its primary structure, a broad range of chemical syntheses of lipid A derivatives have made an enormous contribution to the characterization of lipid A bioactivity, providing novel pharmacological targets for the development of new biomedical therapies. Here, we describe and discuss the chemical aspects regarding lipid A and its role in innate immunity, from the (bio)synthesis, isolation and characterization to the molecular recognition at the atomic level.     

Enantioselective synthesis of rumphellaone A via epoxy nitrile cyclization

The first enantioselective synthesis of rumphellaone A, a cytotoxic 4,5-seco-caryophyllane derivative incorporating a γ-lactone ring as its structural feature, has been achieved by using base-induced intramolecular cyclization of an epoxy nitrile intermediate to install its cyclobutane skeleton as well as three contiguous stereocenters as the key transformation.     

植物聚多糖葡甘聚糖的性质与应用

全面介绍了魔芋的主要成分———葡甘聚糖 (KonjacGlucomannan简称KGM)的结构、提纯方法、物理化学性质和其在医药卫生领域的保健功能及药用价值 ;综述了近年国内外的研究开发现状和其在食品、化工、纺织、医药、石油钻探等领域的应用 ,从而展示了KGM这一丰富的可再生资源的学术研究价值以及在医药、化工、纺织等领域中的广阔的应用前景     

Epoxidation of olefins by hydroperoxo-ferric cytochrome P450

The T252A mutant of cytochrome P450cam is unable to form the oxoferryl "active oxygen" intermediate, as judged by its inability to hydroxylate its normal substrate, camphor. In the present study, we demonstrate that T252A P450cam is nonetheless able to epoxidize olefins, due to the action of a second oxidant. However, as shown in earlier radiolytic studies and by the ability of T252A to reduce dioxygen to hydrogen peroxide, the mutant retains the ability to form the hydroperoxo-ferric reaction cycle intermediate. The present results provide strong evidence that hydroperoxo-ferric P450 can serve as a second electrophilic oxidant capable of olefin epoxidation.     

Stereochemical assignment of the fungal metabolite xestodecalactone A by total synthesis

The first synthesis of the macrocyclic natural product xestodecalactone A, a metabolite of a sponge-derived fungus, is described. By the use of methyl 5-hydroxyhexanoate in its R- or S-configured form, or as its racemate as the precursors, both enantiomers of xestodecalactone A as well as the racemic compound were obtained. Comparison of these synthetic products with the natural product by circular dichroism (CD) spectroscopy and by HPLC on a chiral phase revealed the natural product to have the (R)-configuration.     

Characterization of rhinovirus subviral A particles via capillary electrophoresis, electron microscopy and gas-phase electrophoretic mobility molecular analysis: Part I

During infection, enteroviruses, such as human rhinoviruses (HRVs), convert from the native, infective form with a sedimentation coefficient of 150S to empty subviral particles sedimenting at 80S (B particles). B particles lack viral capsid protein 4 (VP4) and the single-stranded RNA genome. On the way to this end stage, a metastable intermediate particle is observed in the cell early after infection. This subviral A particle still contains the RNA but lacks VP4 and sediments at 135S. Native (150S) HRV serotype 2 (HRV2) as well as its empty (80S) capsid have been well characterized by capillary electrophoresis. In the present paper, we demonstrate separation of at least two forms of subviral A particles on the midway between native virions and empty 80S capsids by CE. For one of these intermediates, we established a reproducible way for its preparation and characterized this particle in terms of its electrophoretic mobility and its appearance in transmission electron microscopy (TEM). Furthermore, the conversion of this intermediate to 80S particles was investigated. Gas-phase electrophoretic mobility molecular analysis (GEMMA) yielded additional insights into sample composition. More data on particle characterization including its protein composition and RNA content (for unambiguous identification of the detected intermediate as subviral A particle) will be presented in the second part of the publication.     

Photoresponsive oil sorbers

A photoresponsive oil sorber (POS) with a hydrophobic, photoresponsive core and shell has been synthesized via suspension polymerization. Lauryl acrylate, isodecyl acrylate, and tert‐butylstyrene were used as monomers, 4‐(methacrylamino)azobenzene (Azo‐M) used as photoresponsive monomer, and bis(methacryloylamino)azobenzene (Azo‐CL‐M) used as photoresponsive surface crosslinker. The POS prefers nonpolar solvents. It absorbed 15 times its dry weight in toluene, 19 times its dry weight in chloroform, and 16 times its dry weight in dichloromethane. Rapid and photoresponsive desorption of solvent (86% of solvent expulsed in 30 min) was characteristic. POS is an excellent gasoline absorber rapidly increasing its body weight in its presence. The new POS is less dense than water, and can potentially be used for cleaning oil spills on water. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 55–62, 2010     

Chemoenzymatic synthesis of the polyketide macrolactone 10-deoxymethynolide

The polyketide synthase-derived pikromycin thioesterase (Pik TE) is unique in its ability to catalyze the cyclization of 12- and 14-membered macrolactones. In this investigation, the total synthesis of the natural hexaketide chain elongation intermediate as its N-acetyl cysteamine (NAC) thioester has been achieved, and its reaction with Pik TE demonstrated the ability of Pik TE to catalyze its macrolactonization to the natural product 10-deoxymethynolide. A steady-state kinetic analysis of the hexaketide chain intermediate with Pik TE was done. A preliminary substrate specificity study with unnatural hexaketide analogues was accomplished, demonstrating the importance of total synthesis in obtaining access to advanced polyketide intermediates. The results show the sensitivity of Pik TE to minor substrate modifications, and illustrate the potential use of thioesterases as versatile macrolactonization catalysts.     

A new fungal morphogenic substance,pyrenolide a from Pyrenophorateres

A new ten-membered lactone, pyrenolide A, was identified as a new fungal morphogenic substance and its structure including absolute stereochemistry was elucidated.