Synthesis, Bioactivity and Crystal Structure Analysis of 2-(Benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) Acetamide

A novel benzisothiazolin-3-one derivative, 2-（benzo[d]isothiazol-3-yloxy）-N-（3- cyano-l-（4-fluorophenyl）-lH-pyrazol-5-yl） acetamide （8）, was synthesized from the initial compound benzo[d]isothiazol-3（2H）-one （BIT） 1 and 4-fluoroaniline 3. The structure of the target compound 8 was determined by elemental analyses, IR and 1H NMR. The single crystals of intermediate compound 6 and the target compound 8 were obtained and determined by X-ray diffraction analysis. The preliminary biological activity was also evaluated and the results showed tile target compound exhibited a good anti-microbial activity.

Synthesis and bioactivity of a novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

A novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were synthesized by the condensation of 4-amino-5- [2-(4-chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2,4-triazole with various(un)substituted aromatic acids in the presence of phosphorous oxychloride.These compounds were investigated for their inhibitory activity to E.coli methionine aminopeptidase(EcMetAP1).Some of the tested compounds showed significant inhibitory activity.

Synthesis,Crystal Structure and Bioactivity of N-Phenethyl-4-hydroxy-4-phenyl Piperidine Hydrochloride

A novel compound N-phenethyl-4-hydroxy-4-phenyl piperidine hydrochloride （C19H24ClNO·H2O） has been synthesized and structurally characterized by elemental analysis, IR, ^1H NMR spectra and single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 8.6306（8）, b = 11.0464（10）, c = 19.3221（18）A^°, V = 1842.1（3）A^°^3, Z = 4, Dc =1.211 g/cm^3,μ = 0.217 mm^-1, Mr= 335.86, F（000） = 720, S = 0.973, R = 0.0420 and wR = 0.1009 for 3627 unique reflections with 3157 observed ones （I 〉 2σ（I））. In the crystal, the dihedral angles made by piperidine ring with two benzene rings are 84.8（6） and 62.5（7）°, respectively. Intermolecular O-H…O and O-H…Cl hydrogen bonds involving water molecules form chains along the b axis, which stabilizes the crystal structure. The preliminary bioactivity tests indicated that the title compound has good effect of cellular growth inhibition to K562 cells and potential bioactivity of anti-leukemia.

Synthesis, Crystal Structure and Bioactivity of N-(phenethylcarbamothioyl)cyclopent-1-enecarboxamide

The compound N-（phenethylcarbamothioyl）cyclopent-1-enecarboxamide was synthesized by the reaction of cyclopent-1-enecarbonyl isothiocyanate with phenethylamine in acetone, and its structure was characterized by IR, 1H NMR and X-ray crystal structure determination. The crystal of the title compound belongs to triclinic, space group P1 with a = 6.9500（7）, b = 9.4618（9）, c = 11.3256（11）, α = 71.522（9）, β = 81.830（8）, γ = 89.237（8）o, Z = 2, V = 698.80（12）3, Dc = 1.304 g/cm3, μ = 0.225 mm-1, F（000） = 292, R = 0.0413 and wR = 0.1073 for 1996 observed reflections with I 〉 2σ（I）. Intramolecular N（2）–H（2）···O（1） interactions as well as intermolecular N（2）–H（2）···O（1）, N（1）–H（1）···S（1） and C（12）–H（12）···S（1） hydrogen bonds help to stabilize the crystal structure. X-ray diffraction analysis reveals that the structure of the new compound exhibits a one-dimensional infinite chain-like structure. The cytotoxicity of the compound was investigated by MTT assay. The results show that the compound is toxic to A549 tumor cell.

Synthesis, Crystal Structure and Bioactivity of Ethyl 1-((2-Bromophenyl)carbamoyl)-2-(3,4,5-trimethoxyphenyl) cyclopropanecarboxylate

Many small-molecule compounds were reported as microtubule-inhibitor with potential anticancer activities, such as combretastatin-A4（CA-4） analogue. The title compound which is one novel cyclopropylamide analogue of CA-4, namely as ethyl 1-（（2-bromophenyl）carbamoyl）-2-（3,4,5-trimethoxyphenyl）cyclopropanecarboxylate, has been synthesized and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n with a = 8.8002（6）, b = 11.4525（8）, c = 21.7870（16） ?, b = 93.810（3）o, V = 2190.9（3） ?3, Z = 4, C22H23BrNO6, Mr = 477.32, Dc = 1.447 Mg/cm3, F（000） = 980, λ（Cu Kα） = 1.54178 ?, μ = 2.883 mm–1, R = 0.0691 and wR = 0.1958 for 6420 observed reflections（I > 2σ（I））. Importantly, the compound revealed potential anticancer activities in six cancer cells and could stimulate tubulin polymerization in vitro, indicating that the small-molecule could be selected as a lead compound for the development of microtubule stimulator.

Synthesis of Atrazine-HPCD Inclusion and Its Bioactivity

The inclusion of atrazine with 2-hydroxypropyl-β-cyclodextrin(HPCD) was synthesized by ultrasonic method, and it was characterized by UV, XRD and 1H NMR. The solubility in water and the bioactivity of the inclusion were also studied here. The results indicated that the UV maximum absorption wavelength of the inclusion remained at 223 nm, while its intensity decreased. The XRD peaks of atrazine disappeared, weakened and shifted in the inclusion, and the chemical shift of H-3 and H-5 of cyclodextrin inner cavity led to the upfield. The characterization data showed that the atrazine-HPCD inclusion had already formed. At the same time, the solubility of the atrazineHPCD inclusion in water became 20.08 times as that of atrazine. Moreover, the atrazine-HPCD inclusion had better herbicidal activity. When the concentration of the inclusion was 6.5 mg/mL, the inhibition ratios of the inclusion to taproot length, taproot fresh weight, sprout length and sprout fresh weight of barnyard grass were 66.96%, 57.22%, 70% and 57.53%, respectively, which were all higher than those of atrazine.

Mulberry Diels-Alder-type adducts:isolation,structure,bioactivity,and synthesis

Mulberry Diels-Alder-type adducts(MDAAs)are unique phenolic natural products biosynthetically derived from the intermolecular[4+2]-cycloaddition of dienophiles(mainly chalcones)and dehydroprenylphenol dienes,which are exclusively distributed in moraceous plants.A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980.Structurally,the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups(Types A−H),while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs(Type I).These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures,remarkable biological activities,and synthetic challenges.The present review provides a comprehensive summary of the structural properties,bioactivities,and syntheses of MDAAs.Cited references were collected between 1980 and 2021 from the SciFinder,Web of Science,and China National Knowledge Internet(CNKI).

The synthesis, bioactivity and paramagnetic resonance of angiotensin Ⅱ and its spin labelled derivative

ANGIOTENSIN Ⅱ(Ang Ⅱ) is an important constituent in renin-angiotension system (RAS).The amino acid sequence of Ang Ⅱ is DRVYIHPF. Ang Ⅱ plays an important role both inmaintenance of normal blood pressure and in occurrence of hypertension. Ang Ⅱ binding re-ceptor can induce many kinds of physiological effects. Spin labeling is an effective method thatgreatly deepened the knowledge in structure, movement and interaction of biologicalmolecules. For example, it has been used in studying interaction of antigen and antibody suc-

Ultrasound-assisted synthesis and preliminary bioactivity of novel 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives containing fluorine

Eight novel 5,7-disubstituted-2-{5-methyl-3-（4-trifluoromethylphenyl）isoxazol-4-ylcarbonylimino}-2H-1,2,4-thiadiazolo[2,3- a]pyrimidines were synthesized by multi-step reactions in yields 68-85%.Reactions were carried out either by ultrasound irradiation or conventional method,and found it was faster and more efficient under ultrasonic irradiation.Preliminary herbicidal activities against Echinochloa crus-galli,Digitaria sanguinalis and Chenopodium serotinum were also evaluated by flat-utensil method,and the results indicated that the target compounds exhibited significant activities,some were even higher than the control herbicide.

Syntheses and Bioactivity of 4″-Sulfonate-5-triphenylsilyl Avermectin B_(1a) and Ivermectin B_(1a) Derivatives

Fourteen new derivatives of avermectin B_(1a) and ivermectin B_(1a) were synthesized from C_5-O-triphenylsilyl avermectin B_(1a) and ivermectin B_(1a)(yield from 40% to 83%). Their chemical structures were characterized by means of IR, ()~1H NMR, ()^(13)C NMR and FAB-MS spectrometries. Some of them show excellent insecticidal activity.

A brief overview of classical natural product drug synthesis and bioactivity

Traditional medicines consisting of compounds derived from natural organisms have been used for human health care worldwide since ancient times.Since the last century,huge numbers of bioactive natural entities with diverse chemical scaffolds have been discovered,and some have been explored as clinical medications to treat various diseases.The advent of modern technologies has promoted the discovery of natural product-based pharmaceutical agents.The synthesis of natural products not only paves the way to confirm their molecular structures but also offers the structural modification opportunity to rationally optimize the drug-likeness parameters and evaluate the bioactivity of analogs.By providing a brief overview of a miscellaneous collection of complex natural products synthesis and the efforts of the structure–activity relationship,the present report aims to highlight the impact of chemical synthesis in natural product generation,diversification,bioactivity evaluation,and natural product-based drug development.

Exploration of a Library of Triazolothiadiazines as Potent Plant Growth Promoters: Design, Synthesis, X-ray Diffraction Analysis and Bioactivity Studies

A series of novel 3-methyl-6-aryl-7-aroyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines were designed,synthesized and tested for their antiproliferative activity against HepG2 cell lines in vitro by the standard SRB assay and plant growth regulation activities on wheat(amonocotyledon)and radish(adicotyledon).The results indicated all the title compounds exhibited a very weak antiproliferative activity against HepG2 cell lines in vitro unexpectedly,while showed potent plant growth-regulating activities on both wheat and radish.The crystal structure of trans-4 d was obtained from X-ray diffraction:C18H13N4OSCl3,Mr=439.75,monoclinic system,space group P21/n,a=5.3224(7),b=14.3578(18),c=24.442(3)A,β=94.180(2)°,V=1862.8(4)A3,F(000)=899,Z=4,Dc=1.5679 g/cm^(3),λ=0.71073A,μ=0.621 mm-1 and the final R=0.0382 for 3274 unique reflections with 2851 observed ones(I>2σ(I)).

Recent advances on the synthesis and application of tetrahydro-y-carbolines

Tetrahydro-y-carbolines(THyCs)constitute one of the most important subtypes of indole alkaloids.In addition to being substructures of natural products,these structural motifs and moieties can often be found in pharmaceuticals due to their diverse bioactivities such as antiviral,antibacterial,antifungal,antiparasitic,antitumor,anti-inflammatory,and neuropharmacological activities.Beyond the pharmacological and biological aspects of these scaffolds,they have considerable synthetic applications for the construction of further bioactive compounds,too.The aim of this review is to summarize recent developments in the synthesis of this compound class.

Sol-gel synthesis,properties and protein loading/delivery capacity of hollow bioactive glass nanospheres with large hollow cavity and mesoporous shell

Hollow nanospheres exhibit unique properties and find a wide interest in several potential applications such as drug delivery.Herein,novel hollow bioactive glass nanospheres(HBGn)with large hollow cavity and large mesopores in their outer shells were synthesized by a simple and facile one-pot ultrasound assisted sol-gel method using PEG as the core soft-template.Interestingly,the produced HBGn exhibited large hollow cavity with ~43 nm in diameter and mesoporous shell of ~37 nm in thickness and 7 nm pore size along with nanosphere size around 117 nm.XPS confirmed the presence of Si and Ca elements at the surface of the HBGn outer shell.Notably,HBGn showed high protein loading capacity(~570 mg of Cyto c per 1 g of HBGn)in addition to controlled protein release over 5 d.HBGn also demonstrated a good in vitro capability of releasing calcium(Ca^(2+):170 ppm)and silicate(SiO_(4)^(4-):78 ppm)ions in an aqueous medium over 2 weeks under physiological-like conditions.Excellent in vitro growth of bone-like hydroxyapatite nanocrystals was exhibited by HBGn during the soaking in SBF.A possible underlying mechanism involving the formation of spherical aggregates(coils)of PEG was proposed for the formation process of HBGn.

Effects of Arg26 and Lys27 mutation on the bioactivity of HNTX-Ⅳ

Hainantoxin-Ⅳ(HNTX-Ⅳ)was isolated from the Chinese bird spider Ornithoctorcs hainana and identified as a novel antagonist of tetrodotoxin-sensitive(TTX-S)sodium channels.As revealed by the solution structure of HNTX-Ⅳ solved by two-dimensional nuclear magnetic resonance(2D-NMR),HNTX-Ⅳ adopts an inhibitor cystine knot motif.To check the role of basic residues during HNTX-Ⅳ’s interaction with TTX-S sodium channels,R26A and K27A mutants of HNTX-Ⅳ were constructed by solid-phase chemical synthesis.The synthesized peptides were purified and refolded under optimized oxidation conditions.Correct synthesis and folding were confirmed by MALDI-TOF mass spectrometry and NMR spectroscopy,respectively.Using the whole-cell patch-clamp technique,Lys27 but not Arg26 was identified as a key residue for HNTX-Ⅳ’s bioactivity against TTX-S sodium channels,because R26A-HNTX-Ⅳ showed slightly reduced activity and K27A-HNTX-Ⅳ showed almost no inhibition.

Contemporary synthesis of bioactive cyclobutane natural products

Many cyclobutane natural products have intriguing biological properties that arise from their fascinating chemical structures.Cyclobutane natural products feature a cyclobutane scaffold as the core or as a part of the spirocyclic or fused cyclic core.However,the highly functionalized nature and the inherent stereochemistry of these cyclobutane natural products,which are associated with their biological activities,pose tremendous challenges to their preparation.In this perspective,we present contemporary advancements in synthetic methods and/or strategies en route to the bioactive cyclobutane natural products.We begin by describing the representative bioactive cyclobutane natural products and then focus on illustrative examples of their syntheses reported from 2018 to 2021.These advances will enable efficient syntheses of cyclobutanes of structural and biological importance.

Synthesis and activity of hydroxyethylene peptidomimetic inhibitors of humanβ-secretase

A series of β-secretase peptidomimetic inhibitors with Leu＊Ala hydroxyethylene dipeptide isostere were synthesized and their β-secretase inhibitory activities were measured. The most potent compound N9 showed an inhibitory rate of 59.66% （10 mg/mL）. Compound N9 might be further modified by means of computational chemical methodology.

Synthesis of Novel Antifungal Triazole Compounds

Based on our previous studies of 3D-QSAR, 38 novel objective compounds belonging to 4 series were designed and successfully synthesized directed by the idea of reconstructing the structure of non-pharmacophores while reserving essential ones in triazoles. In vitro pilot studies on their antifungal activities showed that most compounds have inhibitory effects on C.albicans and some inhibit S.cerevisiae also. The effects on C.albicans of 5 compounds are more potent than or equal to that of fluconazole or itraconazole.

Synthesis, X-ray Crystallographic Analysis and Bioactivities of α-Aminophosphonates Featuring Pyrazole and Fluorine Moieties

A series of novel -aminophosphonates containing pyrazole and fluorine moieties was designed and synthesized through ultrasonic-assisted condensation and solvent-free addition reactions. Their structures were verified by IR, ^1H NMR, ^13C NMR and elemental analysis. The crystal structure of diethyl[（4-cyano-1H-pyrazol-3-ylamino）（3,5-difluorophenyl）methyl]phosphonate（4a, C15H17F2N4O3P） was determined by single-crystal X-ray diffraction. Compound 4a crystallizes in the triclinic system, space group P1 with a = 8.381（3）, b = 10.103（5）, c = 11.268（3） A, α= 83.772（19）, β= 74.726（19）, γ= 70.964（18）, V = 869.9（6） 3, Mr = 370.30, Dc = 1.414 g/cm^3, Z = 2, F（000） = 384, = 0.200 mm^-1, MoKa radiation（ = 0.71073 ）, the final R = 0.0487 and w R = 0.0823 for 1582 observed reflections with I 〉 2（I）. X-ray diffraction analysis reveals that there are two planes in 4a, and the dihedral angle is 71.51°. Two intermolecular hydrogen bonds and a face-to-face … stacking interaction are observed in the crystal structure. The compounds were evaluated for their antifungal, antiviral and antitumor activities, respectively. Among them, 4b, 4c, 4g and 4h exhibit good activities on Sclerotium rolfsii Sacc at 200 μg/m L, while 4b, 4c, 4f and 4g possess good anti-TMV activities at 500 μg/m L. Unfortunately, all of the compounds showed weak antitumor activities.