Benzoyl Moiety Research Articles

Polyprenylated Benzoylphloroglucinols Isolated from Garcinia Species and Their Cytotoxic Effects on Cancer Cell Lines.

Polyprenylated benzoylphloroglucinols (PPBPs) make up a group of complex natural products with anticancer potentials that are mainly distributed in Garcinia plants. As part of our intensive exploration on new bioactive substances from this genus, we report two undescribed PPBPs, picrorhizones I (1) and J (2), along with four known analogues (3-6) from the stem bark of Garcinia picrorhiza and Garcinia gracilis. The new structures were elucidated on the basis of spectroscopic analysis, particularly 1D and 2D NMR and HRESIMS, whereas the absolute configurations were determined by a combination of ECD and NMR calculations coupled with a DP4+ probability analysis. Being the least class in genus Garcinia, picrorhizone I possesses a type-A structure with the position of a benzoyl moiety attaching to one of the bridgehead carbons of a bicyclo[3.3.1]nonane skeleton, which differs from its major type-B counterparts. This work also represents the first report on the occurrence of PPBPs in G. gracilis. The cytotoxic evaluation of the isolated compounds revealed that isogarcinol (4) and garciyunnanin L (5) significantly inhibited the growth of KB and Hela S3 cancer cells with IC50 values lower than 10 μM, while 5 was also strongly active against the Hep G2 cancer cell line with an IC50 value of 8.02 μM. Among the B-class derivatives bearing a lavandulyl side chain, cyclization of the moiety in the bicyclic phloroglucinol skeleton enhanced the cytotoxic properties on cancer cells.

Palladium‐Catalyzed Regioselective C(4)−H Fluoroalkoxylation of Indoles Through Weak Chelation Assistance

AbstractInstalling fluoroalkyl motifs into biorelevant indoles is particularly interesting due to their ubiquitous presence in drug molecules. Herein, we demonstrate the regioselective C4 fluoroalkoxylation of indoles using fluoroalcohols via palladium‐catalyzed chelation‐assisted C─H activation. The weak chelating benzoyl moiety at the C3 position acts as a directing group for remote C(4)─H fluoroalkoxylation of diversely substituted indoles. This methodology demonstrates a high level of regioselectivity and tolerates a range of crucial functional groups, yielding diverse trifluoroalkoxylated indoles in moderate to good yields. Removal of directing/protecting groups and further functionalization established the synthetic utility of the methodology. A preliminary mechanistic investigation is conducted by isolating the palladacycle intermediate and performing the deuterium scrambling study.

Two Photocatalytic Pathways for Reductive Dearomatizations of N‐Arylformylindoles by a Visible‐Light Triplet Organocatalyst

AbstractA visible‐light triplet photocatalyst 5‐acetyl‐2‐mercapto‐benzoic acid methyl ester (AcBSH) was developed through introducing acetyl into benzenethiolate to improve the efficiency of intersystem crossing (ISC) and using o‐methoxyformyl to increase the molar extinction coefficient. In the photocatalytic system of AcBSH, the reductive dearomatization of N‐arylformylindoles is achieved to afford the desired indolines in moderate to excellent yields, including both indoles without (1) and with 2‐substituent (2). The 2‐substituent is a steric hindrance for the conjugation between benzoyl and indole moiety, and makes indole 2 and indole 1 exhibit different reduction potentials (Ered) and different triplet energy levels (ΔET). Thereby, two kinds of substrates undergo primarily two photocatalytic pathways: i) successive SET/protonation pathway, which merging photosensitization via triplet‐triplet energy transfer (EnT) and photoinduced SET for substrates 1, and ii) single electron transfer (SET) from the triplet photocatalyst and a concerted hydrogen atom transfer (HAT) process for substrates 2.

Color-Stable Formulations for 3D-Photoprintable Dental Materials.

Color stability is crucial for dental materials to ensure they perfectly match a patient's tooth color. This is particularly challenging in photoresist-based additive manufacturing. Although some studies have addressed this issue, the exact causes of discoloration and ways to minimize it remain unclear. In this study, the intrinsic causes of discoloration in materials intended for 3D printing are investigated by examining thin-film samples (1200 µm) of various compositions, which are stored under different conditions. The samples are evaluated by measuring the UV-Vis absorption spectra at regular intervals to monitor changes. The findings reveal that both the composition of the formulations and the storage conditions significantly influence the discoloration behavior. Furthermore, methods have been developed to reduce or completely prevent discoloration. The use of photoinitiators with sterically demanding benzoyl moieties, as well as the addition of stabilizers, effectively decreases the intensity of emerging discoloration. Furthermore, incorporating the oxidizing agent cumene hydroperoxide (CHP) results in materials that maintain color stability.

Nonpeptidic Irreversible Inhibitors of SARS-CoV-2 Main Protease with Potent Antiviral Activity.

SARS-CoV-2 infections pose a high risk for vulnerable patients. In this study, we designed benzoic acid halopyridyl esters bearing a variety of substituents as irreversible inhibitors of the main viral protease (Mpro). Altogether, 55 benzoyl chloro/bromo-pyridyl esters were synthesized, with broad variation of the substitution pattern on the benzoyl moiety. A workflow was employed for multiparametric optimization, including Mpro inhibition assays of SARS-CoV-2 and related pathogenic coronaviruses, the duration of enzyme inhibition, the compounds' stability versus glutathione, cytotoxicity, and antiviral activity. Several compounds showed IC50 values in the low nanomolar range, kinact/Ki values of >100,000 M-1 s-1 and high antiviral activity. High-resolution X-ray cocrystal structures indicated an important role of ortho-fluorobenzoyl substitution, forming a water network that stabilizes the inhibitor-bound enzyme. The most potent antiviral compound was the p-ethoxy-o-fluorobenzoyl chloropyridyl ester (PSB-21110, 29b, MW 296 g/mol; EC50 2.68 nM), which may serve as a lead structure for broad-spectrum anticoronaviral therapeutics.

2-(4-Nitrophenyl)isothiazol-3(2H)-one: A Promising Selective Agent against Hepatocellular Carcinoma Cells.

Liver cancer ranks among the most prevalent malignancies globally and stands as a leading cause of cancer-related mortality. Numerous isothiazolone derivatives and analogues have been synthesized and investigated for their potential as anticancer agents; however, limited data exist regarding their efficacy against liver cancer. In the present study, two nitrophenyl-isothiazolones, the 5-benzoyl-2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoA) and the 2-(4-nitrophenyl)isothiazol-3(2H)-one (IsoB), were preliminarily investigated for their cytotoxicity against hepatoma human (Huh7) cells as a liver cancer model and Immortalized Human Hepatocytes (IHHs) as a model of non-cancerous hepatocytes. IsoB, derived from IsoA after removal of the benzoyl moiety, demonstrated the highest cytotoxic effect against Huh7 cells with CC50 values of 19.3 μΜ at 24 h, 16.4 μΜ at 48 h, and 16.2 μΜ at 72 h of incubation, respectively. IsoB also exhibited selective toxicity against the liver cancerous Huh7 cells compared to IHH cells, reinforcing its role as a potent and selective anticancer agent. Remarkably, the cytotoxicity of IsoB was higher when compared with the standard chemotherapeutical agent 5-fluorouracil (5-FU), which also failed to exhibit higher toxicity against the liver cancerous cell lines. Moreover, IsoB-treated Huh7 cells presented a noteworthy reduction in mitochondrial membrane potential (ΔΨm) after 48 and 72 h, while mitochondrial superoxide levels showed an increase after 24 h of incubation. The molecular mechanism of the IsoB cytotoxic effect was also investigated using RT-qPCR, revealing an apoptosis-mediated cell death along with tumor suppressor TP53 overexpression and key-oncogene MYCN downregulation.

Synthesis and Biological Evaluation of 3-(2-Benzoyl-4-chlorophenyl)-4H-spiro [indole-3,2-[1,3]thiazolidine]-2,4(1H)- dione Derivatives for Anti-tubercular and Antimicrobial Activities

Objectives: To synthesize a new scaff fold of 3'-(2-Benzoyl-4-chlorophenyl)-4'H-spiro [indole-3,2'-[1,3] thiazolidine]-2,4'(1H)-dione derivatives and to assess the compounds for anti-tubercular and antimicrobial activities. Methods : A new series of 3'-(2-Benzoyl-4-chlorophenyl)-4'H-spiro [indole-3,2'- [1,3] thiazolidine]-2,4'(1H)-dione derivatives were prepared by synthesizing schiff’s bases followed by condensing schiff base with 2-mercaptopropanoic acid in the presence of zinc chloride. Synthesized compounds were characterized by IR, NMR and Mass spectral data. Their antimicrobial, antitubercular and also docking simulations were evaluated. Findings : Compound 3c (floro substituent) showed potent activity against Mycobacterium tuberculosis H37Rv with MIC value of 3.125 µg/ml when compared with standard Isoniazid. Compound 3c, 3d and 3f displayed better antimicrobial activity against used bacterial and fungal species with MIC range of 3-20µg/ml comparable to standard drugs ciprofloxacin and ketoconazole respectively. In silico studies revealed that compound 3c, 3f and 3d had a better binding affinity with M. tuberculosis enoyl-CoA hydratase EchA6 with ΔG values of -9.6kcal/mol, -9.4kcal/mol, and -8.6kcal/mol respectively comparable to isoniazid of -5.4kcal/mol. Compound 3c, 3f and 3d also displayed good binding affinity with DNA gyrase and lanosterol methylase. Novelty : Introducing benzoyl moiety to the thiazolidine ring potentiates the antitubercular and antimicrobial activity of spiro indole derivatives. Keywords: AntiTB, Antimicrobial, Molecular Docking, Spiro indole, Thiazolidine

Limonoids from the fruits of Chisocheton erythrocarpus and their mosquito larvicidal activities

Phytochemical study of the fruits of Chisocheton erythrocarpus (Hiern) allowed the identification of eight undescribed limonoids, namely erythrocarpines O – V (1–6, 7a and 7b), along with seven known compounds. The structures of these compounds were elucidated based on spectroscopic and HRMS data, along with electronic circular dichroism to configure the absolute configuration. Erythrocarpines O and P are γ-hydroxybutenolide analogs of mexicanolide-type limonoids while erythrocarpine Q – V are phragmalin-type limonoids possessing a 1,29-oxymethylene bridge with either benzoyl or cinnamoyl moiety in their structures. Mosquito larvicidal activity revealed that crude DCM extract of C. erythrocarpus possessed a good larvicidal effect against Aedes aegypti larvae in 48 h (LC50 = 153.0 ppm). Subsequent larvicidal activity of isolated compounds indicated that erythrocarpine G (10) and 14-deoxyxyloccensin K (11) were responsible for the enhanced larvicidal effect of the extract, reporting LC50 values of 18.55 ppm and 41.16 ppm, respectively. Moreover, residual activity testing of the crude DCM extract revealed that the duration of its larvicidal effects is up to 14 days, where it maintained a 98 % larval mortality throughout the test period, under laboratory conditions.

Enhancing nonlinear optical responses via Methoxy Positional Isomerism in Chalcone-Based Materials

The functional moieties present in chalcone derivatives play a pivotal role in finely adjusting the thermal, optical, structural, and nonlinear optical (NLO) characteristics of the chalcone material. This paper details the synthesis of chalcone derivatives where three distinct trimethoxy substituents are integrated into the benzoyl moiety through carboxyl bonding with 2-acetyl pyridine. The synthesis employs the Schmidt condensation method, and the resultant samples are subject to scrutiny through FTIR and FT-Raman techniques to ascertain phase purity. The outcomes reveal substantial alterations in the structural, thermal, optical, and NLO attributes of the samples. The electron-donating property of the trimethoxy groups augments electron density within the chalcone molecule, thereby effecting multiple shifts in the material's characteristics. Interestingly, a methoxy group located at positions 2, 4, and 5 forms crystals with centrosymmetric properties. Conversely, relocating the methoxy groups to positions 3, 4, 5, and 2, 4, 6 induces a transformation from centrosymmetric to non-centrosymmetric crystal structures, resulting in a remarkable enhancement of NLO properties, encompassing second and third harmonic generation. Notably, the compound featuring trimethoxy substitution at positions 3, 4, and 5 demonstrates a 27-fold increase in second harmonic generation compared to the urea crystal. The detailed discussion encompasses the intricate relationship between the molecular structure and nonlinear properties, encompassing third harmonic generation.

ANTIOXIDANT ACTIVITY OF QUINOXALYL HYDRAZONES OF 2-HYDROXYIMINO-1,3-DICARBONYL COMPOUNDS

Biosimilarity and pharmacokinetic descriptors were obtained using SwissADME and ADMETlab 2.0 web services. Analysis of the obtained descriptors shows that, according to Lipinski’s rule, quinoxalyl hydrazones of 2-hydroximino-1,3-dioxocompounds may be promising candidates for drug development for oral administration. Analysis of the pharmacokinetic descriptors of the structures studied shows that, according to the in silico predictions, the compounds can penetrate the blood-brain barrier, be absorbed in the gastrointestinal tract, bind to plasma proteins, be rapidly eliminated from target cells and inhibit CYP3A4, CYP1A2, CYP2C19 and CYP2D6 isoenzymes. The antioxidant activity of quinoxalyl hydrazone derivatives with different benzoyl, ester and acetyl moieties has been studied. Pharmacological screening of the obtained compounds was performed in vitro in the model of Fe2+-induced lipid peroxidation. The data of pharmacological screening indicate clearly pronounced inhibition of lipid peroxidation in the system of yolk lipoproteins by the compounds obtained, which indicates a significant contribution of quinoxalone scaffold in the manifestation of antioxidant properties. Variations in the structure of the starting 1,3-dicarbonyl compounds did not result in significant changes in the antioxidant activity of the obtained hydrazones. The compounds obtained can be promising compounds with marked antioxidant activity for further in vivo studies, including investigation of acute and chronic toxicity. The leading compound is tolyl-substituted quinoxalyl hydrazone IIb

Characterization and In Vivo Antiangiogenic Activity Evaluation of Morin-Based Cyclodextrin Inclusion Complexes.

Morin (MRN) is a natural compound with antiangiogenic, antioxidant, anti-inflammatory, and anticancer activity. However, it shows a very low water solubility (28 μg/mL) that reduces its oral absorption, making bioavailability low and unpredictable. To improve MRN solubility and positively affect its biological activity, particularly its antiangiogenic activity, in this work, we prepared the inclusion complexes of MNR with sulfobutylether-β-cyclodextrin (SBE-β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes obtained by the freeze-drying method were extensively characterized in solution (phase-solubility studies, UV-Vis titration, and NMR spectroscopy) and in the solid state (TGA, DSC, and WAXD analysis). The complexation significantly increased the water solubility by about 100 times for MRN/HP-β-CD and 115 times for MRN/SBE-β-CD. Furthermore, quantitative dissolution of the complexes was observed within 60 min, whilst 1% of the free drug dissolved in the same experimental time. 1H NMR and UV-Vis titration studies demonstrated both CDs well include the benzoyl moiety of the drug. Additionally, SBE-β-CD could interact with the cinnamoyl moiety of MRN too. The complexes are stable in solution, showing a high value of association constant, that is, 3380 M-1 for MRN/HP-β-CD and 2870 M-1 for MRN/SBE-β-CD. In vivo biological studies on chick embryo chorioallantoic membrane (CAM) and zebrafish embryo models demonstrated the high biocompatibility of the inclusion complexes and the effective increase in antiangiogenic activity of complexed MRN with respect to the free drug.

Formal γ−C−H Functionalization of Cyclobutyl Ketones: Synthesis of cis‐1,3‐Difunctionalized Cyclobutanes

Abstract1,3‐Difunctionalized cyclobutanes are an emerging scaffold in medicinal chemistry that can confer beneficial pharmacological properties to small‐molecule drug candidates. However, the diastereocontrolled synthesis of these compounds typically requires complicated synthetic routes, indicating a need for novel methods. Here, we report a sequential C−H/C−C functionalization strategy for the stereospecific synthesis of cis‐γ‐functionalized cyclobutyl ketones from readily available cyclobutyl aryl ketones. Specifically, a bicyclo[1.1.1]pentan‐2‐ol intermediate is generated from the parent cyclobutyl ketone via an optimized Norrish‐Yang procedure. This intermediate then undergoes a ligand‐enabled, palladium‐catalyzed C−C cleavage/functionalization to produce valuable cis‐γ‐(hetero)arylated, alkenylated, and alkynylated cyclobutyl aryl ketones, the benzoyl moiety of which can subsequently be converted to a wide range of functional groups including amides and esters.

Formal γ-C-H Functionalization of Cyclobutyl Ketones: Synthesis of cis-1,3-Difunctionalized Cyclobutanes.

1,3-Difunctionalized cyclobutanes are an emerging scaffold in medicinal chemistry that can confer beneficial pharmacological properties to small-molecule drug candidates. However, the diastereocontrolled synthesis of these compounds typically requires complicated synthetic routes, indicating a need for novel methods. Here, we report a sequential C-H/C-C functionalization strategy for the stereospecific synthesis of cis-γ-functionalized cyclobutyl ketones from readily available cyclobutyl aryl ketones. Specifically, a bicyclo[1.1.1]pentan-2-ol intermediate is generated from the parent cyclobutyl ketone via an optimized Norrish-Yang procedure. This intermediate then undergoes a ligand-enabled, palladium-catalyzed C-C cleavage/functionalization to produce valuable cis-γ-(hetero)arylated, alkenylated, and alkynylated cyclobutyl aryl ketones, the benzoyl moiety of which can subsequently be converted to a wide range of functional groups including amides and esters.

Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity

Two new classes of hybrid quinoline–imidazole/benzimidazole derivatives (the hybrid QIBS salts and QIBC cycloadducts) were designed and synthesized to evaluate their anticancer and antimicrobial activity. The strategy adopted for synthesis is straight and efficient, in four steps: N-acylation, N-alkylation, quaternization and a Huisgen 3 + 2 cycloaddition. The in vitro single-dose anticancer assay of forty six hybrid quinoline-benzimidazole compounds reveal that one QIBS salt (11h), has an excellent quasi nonselective activity against all type of cancer cell with an excellent PGI in the area of 90–100% and very good lethality. Three others quinoline–imidazole/benzimidazole hybrids (8h, 12h, 12f) has an excellent selective activity against some cancer cell lines: breast cancer MDA-MB-468 and Leukemia HL-60 TB). The five-dose assay screening confirms that compound 11h possesses excellent anti-proliferative activity, with GI50 in the range of nano-molar, against some cancer cell lines: Leukemia HL-60 TB, Leukemia K-526, Leukemia RPMI-8226, Breast cancer MDA-MB-468, Lung cancer HOP-92 and Ovarian cancer IGROV1. The antibacterial assay indicates that three hybrid QIBS salts (12f, 12c, 12d) have an excellent activity against Gram-negative bacteria E. coli (superior to control Gentamicin) while against Gram-positive bacteria S. aureus only one compound 8i (R2 = -CF3) exhibits a significant activity (superior to control Gentamicin). The MIC assay indicates that two other compounds (11h, 12h) are biologically active to a very low concentration, in the range of nano-molar. We believe that all these excellent assets related to anticancer and antibacterial activities, make from our hybrid quinoline–imidazole/benzimidazole compounds bearing a phenyl group (R2 = –C6H5) in the para (4)-position of the benzoyl moiety a good candidate for future drug developing.

Dioxidomolybdenum(VI) complexes of azo-hydrazones: Structural investigation, DNA binding and cytotoxicity studies

The synthesis of three new dioxidomolybdenum(VI) complexes [MoO2L1-3(X)] (1–3) {where X = EtOH for 1 and 3 and DMSO for 2} of aroylhydrazone ligands (H2L1-3) containing azobenzene moiety have been reported. H2L1-3 has been synthesized from the condensation of 5-(arylazo) salicylaldehyde derivatives with corresponding aroyl hydrazides. The azobenzene functionality was incorporated in the aroylhydrazone systems containing benzoyl, naphthyl and furyl moieties in order to explore their influence if any, on the biological properties of the corresponding molybdenum complexes. All the synthesized ligands and metal complexes were successfully characterized by elemental analysis, IR, UV–vis, NMR spectroscopy and HRMS. Redox properties of the complexes were studied by cyclic voltammetry. Molecular structures of 1–3 have been determined by X-ray crystallography. The electronic spectra of the complexes have been further analysed using time dependent density functional theory (TDDFT). DNA binding studies reveal that the complexes interact with calf-thymus DNA (CT-DNA) with binding constants in the range 104 M−1. The cytotoxicity activity of the complexes against A549 and HCT-15 cell lines has also been explored.

New Deoxyenhygrolides from Plesiocystis pacifica Provide Insights into Butenolide Core Biosynthesis.

Marine myxobacteria present a virtually unexploited reservoir for the discovery of natural products with diverse biological functions and novel chemical scaffolds. We report here the isolation and structure elucidation of eight new deoxyenhygrolides (1–8) from the marine myxobacterium Plesiocystis pacifica DSM 14875T. The herein described deoxyenhygrolides C–J (1–8) feature a butenolide core with an ethyl residue at C-3 of the γ-lactone in contrast to the previously described derivatives, deoxyenhygrolides A and B, which feature an isobutyl residue at this position. The butenolide core is 2,4-substituted with a benzyl (1, 2 and 7), benzoyl (3 and 4) or benzyl alcohol (5, 6 and 8) moiety in the 2-position and a benzylidene (1–6) or benzylic hemiketal (7 and 8) in the 4-position. The description of these new deoxyenhygrolide derivatives, alongside genomic in silico investigation regarding putative biosynthetic genes, provides some new puzzle pieces on how this natural product class might be formed by marine myxobacteria.

Modulating Properties of Piroxicam, Meloxicam and Oxicam Analogues against Macrophage-Associated Chemokines in Colorectal Cancer

The mechanisms underlying the antineoplastic effects of oxicams have not been fully elucidated. We aimed to assess the effect of classic and novel oxicams on the expression/secretion of macrophage-associated chemokines (RTqPCR/Luminex xMAP) in colorectal adenocarcinoma cells, and on the expression of upstream the non-steroidal anti-inflammatory drug (NSAID)-activated genes NAG1, NFKBIA, MYD88, and RELA, as well as at the chemokine profiling in colorectal tumors. Meloxicam downregulated CCL4 9.9-fold, but otherwise the classic oxicams had a negligible/non-significant effect. Novel analogues with a thiazine ring substituted with arylpiperazine and benzoyl moieties significantly modulated chemokine expression to varying degree, upregulated NAG1 and NFKBIA, and downregulated MYD88. They inhibited CCL3 and CCL4, and their effect on CCL2 and CXCL2 depended on the dose and exposure. The propylene linker between thiazine and piperazine nitrogens and one arylpiperazine fluorine substituent characterized the most effective analogue. Only CCL19 and CXCL2 were not upregulated in tumors, nor was CXCL2 in tumor-adjacent tissue compared to normal mucosa. Compared to adjacent tissue, CCL4 and CXCL2 were upregulated, while CCL2, CCL8, and CCL19 were downregulated in tumors. Tumor CCL2 and CCL7 increased along with advancing T and CCL3, and CCL4 along with the N stage. The introduction of arylpiperazine and benzoyl moieties into the oxicam scaffold yields effective modulators of chemokine expression, which act by upregulating NAG1 and interfering with NF-κB signaling.

Heat Shock Proteins HSPA1 and HSP90AA1 Are Upregulated in Colorectal Polyps and Can Be Targeted in Cancer Cells by Anti-Inflammatory Oxicams with Arylpiperazine Pharmacophore and Benzoyl Moiety Substitutions at Thiazine Ring.

Heat shock proteins HSPA1/Hsp70α and HSP90AA1/Hsp90α are crucial for cancer growth but their expression pattern in colorectal polyps or whether they can be modulated by oxicams is unknown. We quantified (RTqPCR) HSPA1 and HSP90AA1 expression in 50 polyp-normal pairs in relation to polyp malignancy potential and examined the effect of piroxicam, meloxicam and five novel analogues on HSPA1 and HSP90AA1 expression (mRNA/protein) in colorectal adenocarcinoma lines. HSPA1 and HSP90AA1 were upregulated in polyps by 3- and 2.9-fold. Expression ratios were higher in polyps with higher dysplasia grade and dominant villous growth pattern, mostly a result of diminished gene expression in normal tissue. Classic oxicams had negligible/non-significant effect on HSP expression. Their most effective analogue inhibited HSPA1 protein and gene by 2.5-fold and 5.7-fold in Caco-2 and by 11.5-fold and 6.8-fold in HCT116 and HSPA1 protein in HT-29 by 1.9-fold. It downregulated HSP90AA1 protein and gene by 1.9-fold and 3.7-fold in Caco-2 and by 2-fold and 5.0-fold in HCT116. HSPA1 and HSP90AA1 are upregulated in colorectal polyps reflecting their potential for malignancy. HSPA1 in cancer cells and, to lesser degree, HSP90AA1 can be reduced by oxicam analogues with thiazine ring substituted via propylene linker by arylpiperazine pharmacophore with fluorine substituents and by benzoyl moiety.

Structure—Activity Relationship of Local Anesthetics Based on Alkynylpiperidine Derivatives

The influence of the nature of the acyl (propionyl and benzoyl) moiety and the piperidine ring C4 substituent on the activity of several alkynylpiperidine derivatives was studied. The presence of an alkyl (hexyl) radical on the triple bond of the piperidine ring C4 substituent in the infiltration anesthesia model had a positive effect on the anesthesia index and the duration of both total and general anesthesia as compared to lidocaine, novocaine, and trimecaine taken as reference drugs. The ester of 4-(octyn-1-yl)piperidol-1-propionic acid was the most active anesthetic among the studied compounds. Modification of the triple bond (exhaustive hydrogenation and hydration) led to a decrease in the duration of anesthesia. The activity of the benzoate was greater than that of the propionate in the propionate-benzoate pair.

Discovery, SAR, and putative mode of action of N-benzyl-2-methoxybenzamides as potential bleaching herbicides.

Herbicides acting on biosynthesis of plant pigments have contributed greatly to weed control in recent years. In our previous studies, 2-methoxybenzamides were discovered as a novel type of lead compound for the development of bleaching herbicides. A total of 67 benzamide analogues were synthesized and evaluated for herbicidal activity. The structure-activity relationship (SAR) revealed that a methoxyl substitution at the 2-position of the benzoyl moiety is essential for the herbicidal activity of benzamide derivatives, and introduction of small substituents at the meta- or para-position of the benzylamine moiety is also beneficial. Compounds 4, 43 and 44 showed 100% inhibition against Abutilon theophrasti and Amaranthus retroflexus at an application rate of 150 g a.i.ha-1 . The relationship between the structure and herbicidal activity of 2-methoxybenzamides was discussed intensively. Compounds 4, 43 and 44 may serve as novel candidates with a bleaching effect. © 2021 Society of Chemical Industry.