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Heterocyclic compounds offer an enormous area for new lead molecules for drug discovery. Till today, efforts are being continuously made to find appropriate treatment for the management of the deadly disease of cancer. Amongst the large number of heterocycles that are found in nature, heterocycles having oxygen obtained noteworthy attention due to their distinctive and pharmacological activities.‘Pyran’ is one of the most significant non-aromatic, sixmembered ring composed of one oxygen atom and five carbon atoms. It is considered a privileged structure since pyran and its related derivatives exhibit a wide spectrum of biological activities. Pyran derivatives are found to have excellent anti-cancer properties against various types of cancer. The present review focussed on the current advances in different types of pyran-based derivatives as anti-cancer agents. Various in vitro (cell based testing), in vivo (animal based testing) models as well as molecular docking along with results are also covered. A subsection describing briefly natural pyran containing anticancer compounds is also incorporated in the review.

Covering: up to 2020 Treatment resistance and drug-induced refractory malignancies pose significant challenges for current chemotherapy drugs. There have been increasing research efforts aimed at developing novel chemotherapeutics, especially from natural products and related derivatives. Natural cytotoxic peptides, an emerging source of chemotherapeutics, have exhibited the advantage of overcoming drug resistance and displayed broad-spectrum antitumor activities in the clinic. This highlight examines the increasingly popular cytotoxic peptides from isolated natural products. In-depth review of several peptides provides examples for how this novel strategy can lead to the improved anti-tumor effects. The mechanisms and current application of representative natural cytotoxic peptides (NCPs) have also been discussed, with a particular focus on future directions for interdisciplinary research.

Chemical exploration of mangrove-rhizosphere-associated fungus Emericella sp. strain SWR1718 (Aspergillaceae) was performed through various chromatographic workup procedures. The achieved results afforded one new natural compound, emericelactone E (1) in addition to known compounds (2–7). The planar structures of the purified compounds were unambiguously carried out using several spectroscopic methods. Both relative and absolute configurations of compound 1 were carefully determined based on NOESY experiments, coupling constants and comparing its optical rotation with related congeners. Moreover, a plausible biosynthetic pathway of 1 and its related derivatives is reported for the first time in our study. The cytotoxic potential of isolated metabolites was assessed toward three human tumor cell lines where some of them exhibited moderate activities compared to paclitaxel as a standard anticancer.

New fluorine compounds bearing 4-amino-1,2,4-triazino[4,3-b] − 1,2,4-triazin-8-one (4) and the related derivatives N-acyl, N-alkyl, and Schiff base have been obtained from condensation of 6(2′-amin...

The review is dedicated to results of investigations of steroid conjugates published predominantly over the past decade. It consists of three parts in which the data concerning biological activity of steroid conjugates with known drugs, steroid dimers, and steroid conjugates with some natural compounds, their fragments and related derivatives and analogs, are discussed. The structures of 231 steroid conjugates and their anti-cancer properties are presented.

Thymoquinone was recently reported as having a unique pencil-like odor and being the impact compound for the cedar-like and cedar wood-based product smell such as pencils. The compounds thymol and carvacrol are structurally related odorants commonly found in plants and foods such as thyme and oregano, also having a significant contribution to their overall aroma. However, a systematic elucidation of the sensory properties in this class of oxygenated, aromatic monoterpenoids has not been carried out. To close this gap and gain new insights into structure-odor relationships leading to pencil-like and woody odors, 19 structurally related derivatives of p-cymene starting from thymol and carvacrol were synthesized and characterized. The compounds had odor thresholds ranging from 2.0 ng/L air to 388.8 ng/L air, being lowest for thymol and carvacrol and highest for thymohydroquinone. The compounds smelled mostly thyme-like, oregano-like, and pencil-like with phenolic, earthy, and medicinal variations in their odor character, which could be successfully linked to structural motifs.

Phosphite-based Au(I) catalytic systems containing an array of structurally diverse polyether-based regulation sites were designed and synthesised. These catalysts have been successfully tested in the Au(I)-catalysed C–H functionalisation of phenols and related derivatives with gold–carbenes derived from diazo compounds. Regulation of the steric congestion around the catalytic Au(I) centre via ion–dipole interactions with an external regulation agent led to an enhancement of both the activity and selectivity of the reaction. This new approach in supramolecular gold(I) catalysis has been applied to the derivatisation of an array of substituted phenols and related substrates and to the preparation of an advanced synthetic intermediate of the anticancer agent tamoxifen. The effects of the regulation agent on the selectivity and yield of the reaction have been studied and rationalised using DFT-D calculations.

Proline is a natural amino acid that can be considered as an excellent, efficient, and versatile organocatalyst for various asymmetric reactions. The encapsulation of organocatalysts, such as proline and related derivatives, into a porous material, can not only construct a novel heterogeneous catalyst but also provide a platform to mimic and explore the catalytic processes in a biological system. In this regard, metal–organic frameworks (MOFs) and covalent-organic frameworks (COFs) show superiority because of their crystalline structure, rational designable and tunable framework. In this review, we mainly focus on chiral pyrrolidine functionalized MOFs and COFs; the synthetic strategies and related applications of these materials have been summarized systematically.

Fe de erratas del artículo Antineoplastic activity of products derived from cellulose-containing materials: levoglucosenone and structurally-related derivatives as new alternatives for breast cancer treatment. Fil: Delbart, Damian Ignacio. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Área Investigación; Argentina. Fil: Giri, Germán Francisco. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina. Fil: Cammarata, Agostina. Comisión Nacional de Energía Atómica. Gerencia de Investigación y Aplicaciones; Argentina. Fil: Pan, Melisa Denise. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Unidad de Transferencia Genética; Argentina. Fil: Bareño, Lizeth Ariza. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Área Investigación; Argentina. Fil: Amigo, Natalia Loreley. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Área Investigación; Argentina. Fil: Bechis, Andrés. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Área Investigación; Argentina. Fil: Suarez, Alejandra Graciela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina. Fil: Spanevello, Rolando Ángel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (IQUIR-CONICET); Argentina. Fil: Spanevello, Rolando Ángel. Consejo Nacional de Investigaciones Científicas y Técnicas. Scientific Research Career; Argentina. Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Unidad de Transferencia Genética; Argentina. Fil:Villaverde, Marcela Solange. Consejo Nacional de Investigaciones Científicas y Técnicas. Scientific Research Career; Argentina. Fil: Todaro, Laura Beatriz. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Área Investigación; Argentina. Fil: Todaro, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Scientific Research Career; Argentina. Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Instituto de Oncología Ángel H. Roffo. Área Investigación; Argentina. Fil: Urtreger, Alejandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Scientific Research Career; Argentina.

Two new meroterpenoids, aperterpenes N (1) and O (2), along with two known structurally related derivatives, terretonins A (3) and G (4), were isolated and identified from the marine algal-derived endophytic fungus Aspergillus terreus EN-539. Their structures and absolute configurations were determined by a detailed interpretation of spectroscopic data and by X-ray crystallographic analysis. This is the first establishment of the absolute configurations for terretonins A (3) and G (4). Compound 1 showed inhibitory activity against influenza neuraminidase (IC50 = 18.0 nM), and compound 4 showed inhibitory activity against Micrococcus luteus and Staphylococcus aureus, with MIC values of 32 and 8 μg/mL, respectively.

Water plays a crucial role in organic synthesis. However, diversified functionalization manipulated by water is still rare and remains unexplored. Herein, we report the first water-manipulated protocol to achieve the diversified functionalization of tetrahydro-β-carbolines (THβCs) in an open flask at room temperature that exhibit a broad functional-group tolerance. More water leads to monoarylation, while less water leads to diarylation. Further one-step transformation afforded oxidized bis(indolyl)methanes, eudistomin U, and the related derivatives in satisfactory yields.

Lipoarabinomannan (LAM), mannosyl LAM (ManLAM), and mycolyl-arabinogalactan (mAG) are unique and ubiquitous cell wall constituents of Mycobacterium tuberculosis (M. tb), the bacterium causi...

α-Hydroxyphosphonates have been in the focus of interest for many years due to their potential in biological activity. Not only α-hydroxyphosphonates are of general importance, but also the...

Background: Thiazole is widely investigated bioactive scaffold and dynamic tool in medicinal chemistry research. Significance of thiazole compounds are well documented as thiazole is an obligatory structure of number of currently available therapeutics. In spite of that, thiazole derivatives are endowed with myriad biological activities, such as antiviral, anticancer, antibacterial, antifungal, antimalarial, antiparkinsonian, anti-inflammatory activities and many more. Methods: In recent past, different approaches have been introduced for synthesis of thiazole and related compounds. Intrinsic molecular interaction between newly synthesized thiazole compounds and plethora of drug targets/enzymes has rendered discovery of new drug molecules with advances in modes of action. A renewed interest in therapeutic use of thiazole derivatives has been seen among the prospective researchers as exemplified by influx of huge scientific articles and patents. Some important patents of anti-infective and anticancer interest have been addressed appropriately and are presented in tables. Results: This review paper is a contemporary approach on therapeutic/applications of thiazole derivatives by summarizing important patents filed from 2000-2017. The main focus of these patents is on anti-infective and anticancer potential of thiazole based compounds. Conclusion: These approaches may provide valuable information for the further design of more active biological agents through various modifications and derivatizations.

Surugamides are a group of non-ribosomal peptides isolated from marine-derived Streptomyces. Surugamide A (1) and its closely related derivatives, surugamides B-E (2-5), are D-amino acid containing cyclic octapeptides with cathepsin B inhibitory activity. The D-isoleucine (Ile), the nonproteinogenic amino acid residue embedded in 1, is less common in natural peptides because a rare Cβ-epimerization is required for its biosynthesis. Taking advantage of the synthetic route of 2 previously established by our group, we synthesized the cyclic octapeptide 1 containing D-Ile by solid phase peptide synthesis. The structure of 1 actually contains D-allo-Ile in place of D-Ile, which was corroborated by chemical syntheses and chromatographic comparisons.

Aromatic secondary amines (Ar-SAs), constituted of several analogues with varied substitutions in molecular structure, are among the most frequently used anthropogenic antioxidants. Despite the reported toxicity effects, little information is available on their environmental contamination, except for few particular congeners such as diphenylamine. In this study, the occurrence of two kinds of Ar-SAs, substituted diphenylamines (S-DPAs) and novel substituted p-phenylenediamines (S-PPDs), was investigated in dust samples collected from outdoor rubber playgrounds and residential houses. Seven S-DPAs (GM: 102 ng/g) and two S-PPDs (GM: 20.9 ng/g) were detected in indoor dust. Significantly higher concentrations of S-DPAs (GM: 422 ng/g) and S-PPDs (GM: 31.6 ng/g) were observed in playground dust (p < 0.05). Different dominant Ar-SA congeners were found for indoor dust (low molecular weight Ar-SAs) and playground dust (high molecular weight Ar-SAs), indicating varied sources of Ar-SAs for different dust matrices. Apart from these parent chemicals, three diphenylamine derivatives, including N-nitrosodiphenylamine, 2-nitrodiphenylamine, and 4-nitrodiphenylamine, were also confirmed in indoor dust (GM: 35.7 ng/g) and playground dust (GM: 7.88 ng/g). A preliminary estimated daily intake calculation via dust ingestion indicated no immediate health risk to Chinese population. To our knowledge, this is the first report on the occurrence of a wide range of Ar-SAs and related derivates in dust matrices.

Amphetamine and its related derivatives have stimulant and hallucinogenic properties. Illegal use of these drugs is an increasing global problem resulting in significant public health and legal problems. Deaths have been reported after intake of these drugs due to overdose. It is important to determine the type and concentration of illicit drugs in biological samples. These compounds are found in complex matrices at low concentration levels. The microextraction techniques are dominant sample preparation procedure and they are widely accepted as the most labor-intensive part of the bioanalytical process. For this purpose, a survey of recent published advances in microextraction procedures for quantification of amphetamines in biological samples found in the different databases from 2008 to date will be conducted.

The photophysical properties of naturally occurring chlorophylls depend on the regioisomeric nature of the β-pyrrolic substituents. Such systems are the "gold standard" by which such effects are judged. However, simple extrapolations from what has been learned with chlorophylls may not be appropriate for other partially reduced porphyrinoids. Here we report the synthesis of a series of cis/trans-porphodilactones (cis/trans-1) and related derivatives (cis/trans 2-5) designed to probe the effect of regioisomeric substitution in porphyrinoids that incorporate degrees of unsaturation through the β-pyrrolic periphery that exceed those of chlorophyll. These test systems were obtained through β-pyrrolic modifications of the tetrapyrrolic core, which included reduction of β-diazalone to the corresponding dilactol moieties and 1,3-dipolar cycloadditions. In the case of cis- vs. trans-3 bearing two pyrrolidine-fused β-rings we found an unprecedented ΔQL up to ca. 71 nm (2086 cm-1), where ΔQL (QL means the lowest energy transfer band, also the S0 → S1 transition band, which is often assigned as Qy(0,0) band) refers to the transition energy difference between the corresponding cis/trans-isomers. The ΔQL values for these and other systems reported here were found to depend on the differences in the HOMO-LUMO energy gap and to be tied to the degeneracy and energy level splitting of the FMOs, as inferred from a combination of MCD spectral studies and DFT calculations. The aromaticity, estimated from the chemical shifts of the N-H protons and supported by theoretical calculations (e.g., AICD plots and NICS(1) values), was found to correlate with the extent of porphyrin periphery saturation resulting from the specific β-modifications. The aromaticity proved inversely proportional to the degree to which the regioisomerism affected the photophysical properties as noted from plots of ΔQLs in cm-1vs. the average NICS(1) values for 1-5. Such a finding is not something that can be easily interpolated from prior work and thus reveals how aromaticity may be used to fine-tune photophysical effects in reduced porphyrinoids.

Acylation reactions are of crucial importance in synthesis since they provide access to ketones or related derivatives. The well known acylations of aromatics (the Friedel–Crafts reaction) or olefins are commonly carried out under harsh and/or non-sustainable conditions. An alternative approach consists in the use of acyl (or related) radicals as acylating agents. Recently, the photochemical approach has been proposed as a green route for the generation of acyl/alkoxycarbonyl/carbamoyl radicals and their application in synthesis due to the mildness of the conditions employed. The reactions are mostly carried out at room temperature by using inexpensive visible or solar light. This article offers an overview on the photochemical/photocatalyzed pathways that allow the introduction of the acyl group in aromatics, alkenes and alkynes.

The unusual α-amino, β-hydroxy acid MeBmt is a key structural feature of cyclosporin A, an important naturally occurring immunosuppressant and antiviral agent. We present a convergent synthesis of MeBmt which relies on new aspects of dynamic kinetic resolution (DKR) to establish simultaneously the chirality at C(2) and C(3). We also show that this route is applicable to the synthesis of other derivatives.

The Kabachnik–Fields reaction, comprising the condensation of an amine, oxo compound and a P-reagent (generally a >P(O)H species or trialkyl phosphite), still attracts interest due to the challenging synthetic procedures and the potential biological activity of the resulting α-aminophosphonic derivatives. Following the success of the first part (Molecules 2012, 17, 12821), here we summarize the synthetic developments in this field accumulated in the last decade. The procedures compiled include catalytic accomplishments as well as catalyst-free and/or solvent-free “greener” protocols. The products embrace α-aminophosphonates, α-aminophosphinates, and α-aminophosphine oxides along with different bis derivatives from the double phospha-Mannich approach. The newer developments of the aza-Pudovik reactions are also included.

In recent years, a variety of new designs of coronene-based polycyclic aromatic hydrocarbons (PAHs) with diverse functions have emerged to serve as complementary materials in organic chemistry and materials chemistry. In the present review, we highlight the modern aspects of syntheses related to or different from the strategies used in the early era of coronene research. Systematic extension and expansion of coronene backbones to wide categories of angular PAHs are covered. The substitution and extension of coronene architectures, by incorporating functional groups and by fusing small and large conjugated units, advatangeously enrich their photophysical, electrochemical, self-assembling, and other properties, of which are discussed to demostrate their impact in materials chemistry. While the highly symmetric coronenes, tribenzocoronenes and hexabenzocoronenes conceived wide potential in charge-transporting, electroluminescent, sensing, and other applications, other related derivatives such as dibenzo, tetrabenzo and pentabenzocoronenes also displayed their potentials as exemplified by their use as charge-conduction channel in transistor application.

International audience; Given the ubiquitous role of porphyrins in natural systems, these molecules and related derivatives such as phthalocyanines are fascinating building units to achieve functional porous materials. Porphyrin-based MOFs have been developed since the past three decades, yet chemically robust frameworks, necessary for applications, have been achieved much more recently and this field is expanding. This progress is partially driven by the development of porphyrins and phthalocyanines bearing alternative coordinating groups (phosphonate, azolates, phenolates…) that allowed to move the related MOFs beyond metalcarboxylates and achieve new topologies and properties. In this perspective article we first give a brief outline of the synthetic pathways towards simple porphyrins and phthalocyanines bearing these complexing groups. The related MOF compounds are then described; their structural and textural properties are discussed, as well as their stability and physical properties. An overview of the resulting nets and topologies is proposed, showing both the similarities with metal-carboxylate phases and the peculiarities related to the alternative coordinating groups. Eventually, the opportunities offered by this recent research topic, both in term of synthesis pathways, modulation of pore size and shape, stability and physical properties, are discussed

A diversity-oriented strategy was developed for the synthesis of glycosphingolipids (GSLs). This strategy was highlighted by using a simple lactoside containing the core structures of GSL glycan and lipid as the universal starting material to obtain different synthetic targets upon stepwise elongation of the glycan via chemical glycosylations and on-site remodeling of the lipid via chemoselective cross-metathesis and N-acylation. The strategy was verified with the synthesis of a lacto-ganglio GSL, LcGg4, which is a biomarker of undifferentiated malignant myeloid cells, and a series of its analogues or derivatives carrying different sugar chains and unique functionalities or molecular labels. This synthetic strategy should be widely applicable and, therefore, be utilized to rapidly access various GSLs and related derivatives by using different donors for glycosylations and different substrates for lipid remodeling following each glycosylation.

The demand for valuable products from dinoflagellate biotechnology has increased remarkably in recent years due to their many prospective applications. However, there remain many challenges that need to be addressed in order to make dinoflagellate bioactives a commercial reality. In this article, we describe the technical feasibility of producing and recovering amphidinol analogues (AMs) excreted into a culture broth of Amphidinium carterae ACRN03, successfully cultured in an LED-illuminated pilot-scale (80 L) bubble column photobioreactor operated in fed-batch mode with a pulse feeding strategy. We report on the isolation of new structurally related AMs, amphidinol 24 (1, AM24), amphidinol 25 (2, AM25) and amphidinol 26 (3, AM26), from a singular fraction resulting from the downstream processing. Their planar structures were elucidated by extensive NMR and HRMS analysis, whereas the relative configuration of the C-32→C-47 bis-tetrahydropyran core was confirmed to be antipodal in accord with the recently revised configuration of AM3. The hemolytic activities of the new metabolites and other related derivatives were evaluated, and structure–activity conclusions were established. Their isolation was based on a straightforward and high-performance bioprocess that could be suitable for the commercial development of AMs or other high-value compounds from shear sensitive dinoflagellates.

β-Carboline alkaloids are a remarkable family of natural and synthetic indole-containing heterocyclic compounds and they are widely distributed in nature. Recently, these alkaloids have been in the focus of interest, thanks to their diverse biological activities. Their pharmacological activity makes them desirable as sedative, anxiolytic, hypnotic, anticonvulsant, antitumor, antiviral, antiparasitic or antimicrobial drug candidates. The growing potential inherent in them encourages many researchers to address the challenges of the synthesis of natural products containing complex β-carboline frameworks. In this review, we describe the recent developments in the synthesis of β-carboline alkaloids and closely related derivatives through selected examples from the last 5 years. The focus is on the key steps with improved procedures and synthetic approaches. Furthermore the pharmacological potential of the alkaloids is also highlighted.

We evaluate the empirical validity of the compound option framework. In a model where corporate securities are options on a firm's assets, option contracts on these can be viewed as options on options, or compound options. We estimate a model with priced asset variance risk and find that it jointly explains the level and time variation of both equity index (SPX) and credit index (CDX) option prices well out-of-sample. This suggests that the two options markets are priced consistently, contrary to recent findings. We show that variance risk is important for establishing pricing consistency between equity, credit, and related derivatives.

This note explores a secondary effect of the GameStop short squeeze event and links the exalted focus of retail investors on meme stocks to financial literacy and autodidacticism. From an overview of stylized facts about the short squeeze of GameStop based on high frequency data, short interest, and key figures of related derivatives, it is shown that these financial concepts are reflected in keyword searches across multiple platforms. This self-education with regard to financial terms, keywords, and products and the understanding of basic market speculation mechanisms such as short sales plays a significant role for the influx of retail investors.

A diversity-oriented strategy combining enzymatic glycan assembly and on-site lipid remodeling via chemoselective cross-metathesis and N-acylation was developed for glycosphingolipid (GSL) synthesis starting from a common, simple glycoside. The strategy was verified with a series of natural GSLs and GSL derivatives and showed several advantages. Most notably, it enabled two-way diversification of the glycan and lipid, including introduction of designed molecular tags, to provide functionalized GSLs useful for biological studies and applications.

Due to their physical and chemical characteristics, anthocyanins are amongst the most versatile groups of natural compounds. Such unique signature makes these compounds a focus in several different areas of research. Anthocyanins have well been reported as bioactive compounds in a myriad of health disorders such as cardiovascular diseases, cancer, and obesity, among others, due to their anti-inflammatory, antioxidant, anti-diabetic, anti-bacterial, and anti-proliferative capacities. Such a vast number of action mechanisms may be also due to the number of structurally different anthocyanins plus their related derivatives. In this review, we highlight the recent advances on the potential use of anthocyanins in biological systems with particular focus on their photoprotective properties. Topics such as skin aging and eye degenerative diseases, highly influenced by light, and the action of anthocyanins against such damages will be discussed. Photodynamic Therapy and the potential role of anthocyanins as novel photosensitizers will be also a central theme of this review.

A study of acyl protecting groups derived from the Ph* motif is reported. While initial studies indicated that a variety of functional groups were not compatible with the Br2-mediated cleavage conditions required to release the Ph* group, strategies involving the use of different reagents or a modification of Ph* itself (Ph*OH) were investigated to solve this problem.

Quinoline, isoquinoline, and indoles are common heterocyclic compounds. They have many biological activities, such as antioxidant, anti-inflammatory, antibacterial, antitumor, anti-virus, anti-rheumatism, immunity regulation, expectorant, and analgesic. Over the past few centuries, traditional natural products have made great contributions to the discovery and development of new therapeutic agents. Many important drugs have been found from these three classes of compounds. In this mini-review, we mainly cover the research progress on antioxidant, anti-inflammatory, antibacterial, analgesic activities of quinoline, isoquinoline, and indole compounds over the past 20 years (2000- 2019). We aim to explore new characteristic groups or structures in the search for active lead compounds and provide a basis for rational drug design.

The two-step acidic hydrolysis of &alpha, hydroxybenzylphosphonates and a few related derivatives was monitored in order to determine the kinetics and to map the reactivity of the differently substituted phosphonates in hydrolysis. Electron-withdrawing substituents increased the rate, while electron-releasing ones slowed down the reaction. Both hydrolysis steps were characterized by pseudo-first-order rate constants. The fission of the second P-O-C bond was found to be the rate-determining step.

Cholesterol, steroid alcohol, was discovered by M.E. Chevreul in 1815. Cholesterol and its derivatives showed a large variety of biological properties such as anticancer activity, anticardiac activity, anti-inflammatory activity, antimicrobial activity, anti-psychotic activity, antioxidant activity, drug-loaded activity, etc. In this mini-review, the advances of structural modification of cholesterol from 2014 to 2020 are summarized. In addition, the bioactivities, mechanisms of action and structureactivity relationships of cholesterol and its related derivatives are also discussed.

Natural products and their related derivatives play a significant role in drug discovery and have been the inspiration for the design of numerous synthetic bioactive compounds. With recent advances in molecular biology, numerous engineering tools and strategies were established to accelerate natural product synthesis in both academic and industrial settings. However, many obstacles in natural product biosynthesis still exist. For example, the native pathways are not appropriate for research or production; the key enzymes do not have enough activity; the native hosts are not suitable for high-level production. Emerging molecular biology tools and strategies have been developed to not only improve natural product titers but also generate novel bioactive compounds. In this review, we will discuss these emerging molecular biology tools and strategies at three main levels: enzyme level, pathway level, and genome level, and highlight their applications in natural product discovery and development., Highlights • Discovery and development of bioactive natural products remain a challenge. • Many molecular biology tools have been developed for natural product synthesis. • Tools implemented at enzyme, pathway, and genome levels will be discussed. • Important applications of emerging molecular biology tools will be highlighted.

Two equations are considered in this paper&mdash, the Black&ndash, Scholes equation and an equation that models the spatial dynamics of a brain tumor under some treatment regime. We shall call the latter equation the tumor equation. The Black&ndash, Scholes and tumor equations are partial differential equations that arise in very different contexts. The tumor equation is used to model propagation of brain tumor, while the Black&ndash, Scholes equation arises in financial mathematics as a model for the fair price of a European option and other related derivatives. We use Lie symmetry analysis to establish a mapping between them and hence deduce solutions of the tumor equation from solutions of the Black&ndash, Scholes equation.

The paper presents an accurate in silico measurement of the dissociation constant of HCQ on three important SARS-Cov2 protein targets, namely the main protease (3CLpro) and the Papain-like protease (PLpro) and the RNA dependent RNA polimerase (RdRp), using the recently the released PDB stuructures of these protein. Calculations are done using state-of-the art force fields and advanced simulation methodologies combining enhanced sampling and nonequilibrium techniques amenable to massive parallelization on a dedicated HPC cluster.We have shown that HCQ may act as a mild inhibitor for all the three viral proteins, with potency increasing in the series PLpro, 3CLpro, RdRp. By analyzing the bound state configurations, we were able to improve the potency for the 3CLpro target, designing a novel HCQ-inspired compound, named PMP329, with predicted nanomolar activity. If confirmed in vitro, our results provide a convincing molecular rationale for the use of HCQ or of strictly related derivatives in the treatment of Covid-19.

This note presents a preliminary approach to the design of an across-the-curve credit spread index (AXI). The index is a measure of the recent average cost of wholesale unsecured debt funding for publicly listed U.S. bank holding companies and their commercial banking subsidiaries. This may be a useful benchmark for bank lending and related derivatives risk management applications. The index is a weighted average of credit spreads for unsecured debt instruments with maturities ranging from overnight to five years, with weights that reflect both transactions volumes and issuance volumes. We provide preliminary illustrative output of the bond-based component of AXI using TRACE secondary-market price and volume data from 2002–2019. We have only extremely preliminary estimates of the short-maturity (money-market) spread component.

Geim and Novoselov synthesized in 2004 single-atom thick carbon sheet graphene and opened the door for research of 2D carbon materials. Graphene and related derivatives called graphynes as well as nanoribbons have unique electronic, optical, and mechanical properties. However, with the prediction of quasi-planar boron clusters and sheets in 1997, I. Boustani also opened the door for the 2D boron sheets research known nowadays as borophene. The synthesis of borophene encouraged researchers to explore the mechanical, optical, magnetic and electronic properties as well as their potential applications in nanotechnology.

Over the past 3 decades, monoclonal antibodies and their related derivatives, including recently approved antibody-drug conjugates, conquered a central role in cancer therapy because of their contribution to improve survival, time to progression and quality of life of patients compared to chemotherapy protocols. This review summarizes information on approved original and biosimilar products, as well as investigational antibody-based therapeutics, targeting ErbB2. This target has been selected as a paradigmatic example because of its relevant role in sustaining the malignancy of major cancer diseases including, breast, gastric and other chemotherapy-resistant solid tumors. This work analyzes the drivers affecting research and development of next-generation anti-ErbB2 immunotherapeutics, taking into account unmet medical needs and pharmacoeconomic issues related to sustainability. The analysis may help with the design of future research and development strategies.

Fluorine chemistry has represented a hot topic in drug research over the last decade. Because of their pharmaceutical potential, fluorine-containing amino acids and related derivatives have acquired high importance among medicinal chemists. Therefore their synthesis and the development of various synthetic methods for these types of molecular scaffolds have gained increasing interest in synthetic organic chemistry. The current review focuses on synthetic protocols towards fluorine-containing amino acid derivatives through late-stage fluorination with various nucleophilic reagents, describing the access of various open-chain and cyclic α-, β-, γ-amino acid derivatives.

Despite significant coverage in the financial press in recent years, financial engineering by city governments via the use of financial derivatives such as interest rate swaps remain an understudied area of urban financial policy. Indeed, press accounts and other case or conceptual urban studies research emphasizing the downside of these transactions are some of the only sources of information on these instruments. These stories and studies often allude to or speculate on a more basic question: Why would a government choose to enter into a complex financial instrument like a debt-related derivative? This research posits three exploratory hypotheses—financial health, financial experience and/or financial sector influence, and governance structure—culled from media accounts and the urban studies literature on the use of debt-related derivatives by city governments in the United States. It empirically explores these hypotheses by examining the various fiscal, financial, and issuer characteristics of the largest 50 U.S. cities and their choice of whether to use debt-related derivatives. The research finds that the characteristics of government most associated with debt-related derivative use are declining financial condition, increased financial experience and/or financial sector influence, and prior use of interest rate swaps.

Amphetamine and its related derivatives and analogues (ADRA) are highly addictive central nervous system stimulants that are used commonly in the treatment of attention-deficit/hyperactivity disorder and narcolepsy. These medications are associated with many side effects but reports of peripheral arterial manifestations associated with ADRA usage are scarce. We retrospectively reviewed the records of 16 patients (median age 37 years (IQR 31–47), 13 females) referred to a single tertiary referral service while receiving ADRA. Follow-up was available for a median of 3 years (IQR 3–4.5). The most common presentation (62.5%) was mild vasospastic symptoms involving the upper, lower or both extremities. Six patients developed severe manifestations including tissue loss and the need for lower extremity amputation. Most patients (75%) refused to stop the medication during follow-up. Underlying rheumatologic disorders were found in 25% of the patients, and the presence of rheumatologic disease seemed to be associated with more severe vascular manifestations. In conclusion, it is important to search for ADRA usage as part of the differential diagnosis of digital ischemia.

The compounds responsible for the bitter off-taste of processed onion (Allium cepa) were studied. Using a series of sensory-guided HPLC fractionations, the existence of nine groups of hitherto unknown sulfur compounds has been revealed. On the basis of spectroscopic data (MS, NMR, and IR), it was found that these compounds, trivially named allithiolanes A–I, are members of a large family of structurally closely related derivatives of 3,4-dimethylthiolane S-oxide, with the general formulas of CxHyO2S4, CxHyO3S5, and CxHyO4S6 (x = 10–18, y = 18–30). The presence of multiple stereoisomers was observed for each group of allithiolanes. Allithiolanes possess an unpleasantly bitter taste with detection thresholds in the range of 15–30 ppm. Formation pathways of these newly discovered sulfur compounds were proposed.

This article presents a stochastic equilibrium model for environmental markets that allows us to study the characteristic properties of emission permit prices induced by the design of today’s cap-and-trade systems. We characterize emission permits as highly nonlinear contingent claims on economy-wide emissions and reveal their hybrid nature between investment and consumption assets. Our model makes predictions about the dynamics and volatility structure of emission permit prices, the forward price curve, and the implications for option pricing in this market. Empirical evidence from existing emissions markets shows that the model explains the stylized facts of emission permit prices and related derivatives.

Recent advances in stem cell research and nanotechnology have significantly influenced the landscape of tissue engineering and regenerative medicine. Precise and reproducible control of the fate of stem cells and their lineage specification have, therefore, become more crucial than ever for the success of stem cell-based technologies. Extensive research has been geared towards developing materials that are capable of mimicking the physiological microenvironment of stem cells and at the same time, controlling their eventual fate. An interesting example of these materials is two-dimensional graphene and its related derivatives. A high specific surface area coupled with superior chemical stability, biocompatibility, and flexibility in functionalization render graphene-based nanomaterials one of the most exciting platforms for tissue engineering and regenerative medicine applications, especially for stem cell growth, proliferation, and differentiation. In this review, we discuss the love-hate relationship between stem cells and graphene-based nanomaterials in tissue engineering and regenerative medicine. We first discuss the role and importance of stem cells in tissue engineering and regenerative medicine. We then highlight the use of nanomaterials for stem cell control, the interaction between stem cells and graphene nanomaterials as well as their biocompatibility, biodistribution, and biodegradability considerations. We also offer our perspectives on the various challenges and opportunities facing the use of graphene and its derivatives for stem cell growth and differentiation.

The kinetically robust hydride [t-HFe(2)(Me(2)pdt)(CO)(2)(dppv)(2)](+) ([t-H1](+)) (Me(2)pdt(2−) = Me(2)C-(CH(2)S(−))(2); dppv = cis-1,2-C(2)H(2)(PPh(2))(2)) and related derivatives were prepared with (57)Fe enrichment for characterization by NMR, FT-IR, and NRVS. The experimental results were rationalized using DFT molecular modeling and spectral simulations. The spectroscopic analysis was aimed at supporting assignments of Fe–H vibrational spectra as they relate to recent measurements on [FeFe]-hydrogenase enzymes. The combination of bulky Me(2)pdt(2−) and dppv ligands stabilizes the terminal hydride with respect to its isomerization to the 5–16 kcal/mol more stable bridging hydride ([μ-H1](+)) with t(1/2)(313.3 K) = 19.3 min. In agreement with the nOe experiments, the calculations predict that one methyl group in [t-H1](+) interacts with the hydride with a computed CH⋯HFe distance of 1.7 Å. Although [t-H(57)1](+) exhibits multiple NRVS features in the 720–800 cm(−1) region containing the bending Fe–H modes, the deuterated [t-D(57)1](+) sample exhibits a unique Fe-D/CO band at ∼600 cm(−1). In contrast, the NRVS spectra for [μ-H(57)1](+) exhibit weaker bands near 670–700 cm(−1) produced by the Fe–H–Fe wagging modes coupled to Me(2)pdt(2−) and dppv motions.

A hemiaminal derivative identified during preparation of the penultimate of ceftolozane 1, mandated a thorough investigation of the source of the impurity. N,N-Dimethylacetamide (DMAc) subjected to oxidation was found to be the culprit generating oxidized products that serve as sources of the hemiaminal derivative. Identification of DMAc as a source of formaldehyde derivatives and the mechanism of DMAc oxidation are elaborated.