Acid 1a Research Articles

Activation of Secondary Metabolism and Protease Activity Mechanisms in the Black Koji Mold Aspergillus luchuensis through Coculture with Animal Cells.

The activation of secondary metabolism plays a pivotal role in the discovery of novel natural products. We recently developed a coculture method involving actinomycetes and mouse macrophage-like cells to stimulate the production of bioactive compounds. A black koji mold, Aspergillus luchuensis IFM 61405, markedly enhanced the production of (3S,8R)-8-hydroxy-3-carboxy-2-methylenenonanoic acid (1a), (3S,8S)-8-hydroxy-3-carboxy-2-methylenenonanoic acid (1b), and (3S)-9-hydroxy-3-carboxy-2-methylenenonanoic acid (2) when coincubated with J774.1 mouse macrophage cells. The production of 1 and 2 increased by at least 3.5-fold and 2.7-fold, respectively, compared to monoculture after 7 days. A mechanistic investigation revealed that a protease from strain IFM 61405 plays a key role in enhancing the production of 1 and 2. This enhancement was not replicated in A. niger IFM 59706, a nonkoji mold, despite the presence of biosynthetic genes for 1 and 2 in A. niger IFM 59706. Furthermore, the addition of protease inhibitors suppressed the production of 1 and 2, suggesting that proteins secreted from animal cells, likely degraded by proteases secreted by strain IFM 61405, serve as precursors for 1 and 2. The results show that the strategy of coculturing koji mold with animal cells has the potential to enhance the production of natural products.

Virtual and in Vitro Screening Employing a Repurposing Approach Reveal 13-cis-Retinoic Acid is a PTP1B Inhibitor.

Current treatments for type 2 diabetes (T2D) mainly rely on exercise, dietary control, and anti-diabetic drugs to enhance insulin secretion and improve insulin sensitivity. However, there is a need for more therapeutic options, as approved drugs targeting different pharmacological objectives are still unavailable. One potential target that has attracted attention is the protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the insulin signaling pathway. In this work, a comprehensive computational screening was carried out using cheminformatics and molecular docking on PTP1B, employing a rigorous repurposing approach. The screening involved approved drugs and compounds under research as anti-diabetics that bind to targets such as peroxisome proliferator-activated receptor gamma (PPAR-γ) and α-glucosidase. Several computational hits were then meticulously tested in vitro against PTP1B, with 13-cis-retinoic acid (3a) showing an IC50 of 0.044 mM and competitive inhibition. Molecular dynamics studies further confirmed that 3a can bind to the catalytic binding site of PTP1B. Finally, 3a is the first time it has been reported as an inhibitor of PTP1B, making it a potentially valuable candidate for further studies in D2T treatment.

Recognition of carboxylic acids and phosphonic acids using a 1,8-diphenylanthracene-based diguanidine in solution and solid states

A 1,8-diphenylanthracene-based diguanidine 1 has been designed and synthesized for the recognition of carboxylic acids and phosphonic acid derivatives. The diguanidine 1a forms 1:1 complexes with the dicarboxylic acids and the diphosphonic acid derivatives in a DMSO solution, and the formation of these complexes was confirmed by a DOSY NMR analysis. The binding mode towards the guanidyl group (Type I, Type II, two existing types of binding modes toward three nitrogen atoms) with a diphosphonic acid derivative was successfully demonstrated by the 2D NOESY analysis. The diguanidine 1a does not show any fluorescence in a DMSO solution, but after the addition of carboxylic acids, the formation of a stable complex or the formation of the protonated guanidinium (1a+2H+) were distinguishable by the observation of a light-blue fluorescence around 430 nm. These fluorescence observations can be determined the stability of the complexes of the diguanidine 1a with carboxylic acids. On the other hand, the DMSO solution of diguanidine 1a showed a light-blue fluorescence after the addition of phosphonic acids. Interestingly, diguanidine 1a recognized methylphosphonic acid 9a in the solid state by grinding and showed a green fluorescence, while the other phosphonic acids 9 and dicarboxylic acids (4d: pimelic acid, 4f: azelaic acid) showed a light-blue fluorescence in the solid state, and a selectivity was observed. These fluorescence characteristics of the diguanidine 1 are applicable for the detection of carboxylic acids and phosphonic acids, especially for methylphosphonic acid 9a in the solid state.

Cytotoxic and antibacterial compounds from Schinus terebinthifolia Raddi fruits

Chromatographic procedures of extracts of Schinus terebinthifolia Raddi fruits afforded (Z)-masticadienoic (1) and 3β-masticadienolic (2) acids, tetrahydroamentoflavone (3), and 4-O-methyl gallic acid (4). Addicionally, the derivative 6-oxo masticadienoic acid (1a) was prepared by an allylic oxidation. The chemical structures of obtained compounds were elucidated by spectrometric data analyses. Furthermore, both the semi-synthetic derivative and the metabolites were subjected to in vitro cytotoxicity against the A549 human lung cancer cell line, as well as antimicrobial activity tests. Compounds 2 and 1a exhibited cytotoxicity towards A549 cells with IC50 values of 20.13 and 6.11 µM, respectively. In the tests against pathogens, the CHCl3 and EtOAc soluble fractions of MeOH extract along with the pure compounds, exhibited antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Except for 4-O-methyl gallic acid, the other pure compounds showed inhibitory microbial activities with MIC values ranging from 0.25 μg/mL to 25 μg/mL doses.

Synthesis and PASS-assisted evaluation of new heterocyclic compounds containing hydroquinoline scaffolds

Currently, there is a growing interest in the synthesis of heterocyclic compounds containing hydroquinoline fragments. This surge can be attributed to the broad range of pharmaceutical and industrial applications that these compounds possess. In this study, the synthesis of both linear and fused heterocyclic systems that incorporate hydroquinoline fragments was described. Furthermore, the pharmacological activity spectra of the synthesized compounds were predicted using the in silico method, employing the Prediction of Activity Spectra of Substances (PASS) program. Hydroquinolines containing the nitrile functionality 7 and 8 were synthesized through the reaction of the corresponding hydroquinolinecarbaldehyde 5a, 6b with hydroxylamine hydrochloride and iodine in aqueous ammonia under ambient conditions, respectively. 2-Phenyl-1,3-oxazol-5(4 H)-ones 9a, b and 10a, b were synthesized via the condensation of compounds 5a, b and 6a, b with hippuric acid in acetic acid in 30–60% yield. When the methyl activated 7-methylazolopyrimidines 11a, b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a, b, 60–70% yield of triazolo/pyrazolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a, b were obtained. The condensation of 7-hydroxy-1,2,3,4-tetramethyl-1,2-dihydroquinoline 3 h with dimethylacetylenedicarboxylate (DMAD) and ethyl acetoacetate afforded cyclic products 16 and 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene-active compounds such as ethyl cyanoacetate/dimethyl-3-oxopentanedioate/ethyl acetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted coumarins 19 and 21 containing dihydroquinoline moiety. The pentacyclic coumarin 22 was obtained via the tandom condensation reaction of malononitrile with 5e in the presence of a catalytic amount of piperidine in ethanol. The biological activities of the synthesized compounds were predicted using the PASS program. Based on the prognosis, compounds 13a, b, and 14 exhibited a high likelihood of being active as inhibitors of gluconate 2-dehydrogenase, as well as possessing antiallergic, antiasthmatic, and antiarthritic properties, with a probability value (Pa) ranging from 0.849 to 0.870. Furthermore, it was discovered that compounds 7 and 8 tended to act as effective progesterone antagonists and displayed antiallergic, antiasthmatic, and antiarthritic effects (Pa = 0.276–0.827). Among the hydroquinolines containing coumarin moieties, compounds 17, 19a, and 19c were predicted to be potent progesterone antagonists, with Pa values of 0.710, 0.630, and 0.615, respectively.Graphical

Synthesis and characterization of two Cu(II) complexes of new quinoline-based carboxylic acid

A new quinoline-based carboxylic acid called 3-benzoyl-2-oxo-1,2-dihydro-quinoline-4-carboxylic acid (HQC) (1a) was synthesized. In addition, one dimensional polymeric {[Cu(QC)2(BPE)2DMSO]}n.2DMSO.H2O (2) (BPE = 4,4′-ethylenebipyridine, DMSO = dimethyl sulfoxide) and dimeric [Cu2(QC)2(AcO)2(DMSO)2] (3) (QC = 3-benzoyl-2-oxo-1,2-dihydro-quinoline-4-carboxylate, AcO = Acetate ion) two Cu(II) complexes were synthesized by hydrothermal reaction. The structure of 1a was elucidated using elemental analysis and spectral techniques (NMR, UV–Vis and FTIR), while X-ray study, UV–Vis, FTIR, magnetic susceptibility and elemental analysis were used for complexes (2 and 3). X-ray analysis revealed that complex 2 has square-pyramidal geometry and complex 3 has octahedral geometry. From X-ray analysis for one dimensional coordination polymer 2, HQC (1a) was found to have a monodentate coordination mode. In contrast to 2, in dimeric complex 3, QC acts as a bidentate ligand, bridging two Cu(II) atoms.

α-Glucosidase inhibition assay of galbanic acid and it amide derivatives: New excellent semi-synthetic α-glucosidase inhibitors

α-Glucosidase inhibitory activity of galbanic acid and its new amide derivatives 3a–n were investigated. Galbanic acid and compounds 3a–n showed excellent anti-α-glucosidase activity with IC50 values ranging from 0.3 ± 0.3 μM to 416.0 ± 0.2 μM in comparison to positive control acarbose with IC50 value of = 750.0 ± 5.6. In the kinetic study, the most potent compound 3h demonstrated a competitive mode of inhibition with Ki = 0.57 µM. The interaction of the most potent compound 3h with the α-glucosidase was further elaborated by in vitro Circular dichroism assessment and in silico molecular docking and Molecular dynamics studies. Compound 3h was also non-cytotoxic on human normal cells. In silico study on pharmacokinetics and toxicity profile of the most potent galbanic acid derivatives demonstrated that these compounds are valuable lead compounds for further study in order to achieve new anti-diabetic agents.

Effects of competitive cations and dissolved organic matter on ammonium exchange and up-concentration properties of ion exchangers from domestic wastewater under multicycle exchange - regeneration operation

This study aimed to investigate the impact of competitive cations and dissolved organic matter (DOM) on ammonium exchange and up-concentration properties of ion exchangers for domestic wastewater treatment during the multicycle exchange - regeneration operations. Three ion exchangers, including zeolite, strong acid cation resin and 4A molecular sieve (MS), all showed good NH4+ separation and up-concentration properties in 30 exchange - regeneration cycles. The exchange capacities of zeolite, resin, and MS decreased by 8.2 %, 10.4 %, and 4.8 % in the presence of Ca2+ and Mg2+, while DOM only impaired the exchange ability of zeolite. The up-concentration factors of zeolite, resin, and MS were 5.1, 11.5, and 5.0, respectively. Isothermal tests and breakthrough curves confirmed that long-term salt regeneration slightly reduced the exchange capacity, and the presence of competitive cations and DOM shortened the breakthrough time. Elemental mass balance further demonstrated that Ca2+ and Mg2+ were easily trapped by ion exchangers and could be released into the regeneration solution, which should be precipitated to avoid accumulation for long-term cyclic operation. Morphological analysis indicated that the presence of Ca2+ and Mg2+ would cause the resin to crack. Overall, for domestic wastewater treatment, the resin exhibited the highest NH4+ capture ability and up-concentration properties with low resistance to Ca2+ and Mg2+ contamination, while silicate exchangers with a regular and compact structure had higher durability but lower up-concentration properties.

Impression Disinfection and Its Effect on Dimensional Accuracy and Surface Detail in the Times of COVID-19: An In Vitro Study.

Introduction The disinfection of impressions is crucial to eliminate the viral and other microbial loads to prevent the cross contamination of diseases. The aim of this study was to compare the effect of different virucidal disinfecting methods on the dimensional accuracy and surface detail reproduction (SDR) of impression materials. Methods A total of 160 samples were fabricated with different impression materials using zinc oxide eugenol (Group 1), alginate (Group 2), polyether (Group 3), and addition silicone (Group 4) impression materials, each containing 40 samples (n=40). These groups were further divided into Subgroups A, B, C, and D (n=10) based on the disinfecting method used. Disinfection was carried outusing 0.2% peracetic acid (A), a natural polymer of glucosamine (B), ultraviolet (UV) radiation (C), and ozonated water (D). The disinfected impressions were poured in type IV gypsum, and the obtained casts were checked for dimensional accuracy and surface detail reproduction (SDR). For dimensional accuracy, a one-way analysis of variance (ANOVA) test and, for surface detail reproduction, the chi-square test were used to compare the different subgroups of each impression material separately. Results Zinc oxide eugenol samples showed the lowest mean dimensional change when disinfected with 0.2% peracetic acid (1A=154.1 µm), and alginate showed the lowest mean dimensional change when disinfected using ozonated water (2D=134.9 µm). On the other hand, the lowest mean dimensional change observed in polyether and addition silicone samples was those which were disinfected using UV radiation (3C=100.9 µm and 4C=113.5 µm). Surface detail was reproduced adequately in most of the samples. Conclusion A 0.2% peracetic acid could be used to disinfect zinc oxide eugenol impressions, ozonated water for alginate impressions, and UV radiation for polyether and addition silicone impressions.

Identification and quantification of N6-methyladenosine by chemical derivatization coupled with 19F NMR spectroscopy.

N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.

Impact of alkyl chains, electron donor substituents and acidic group on aggregation-induced emission of carboxylic acid functionalized quinoxalines

We report an optical study of quinoxaline-based luminogens derived from 2,3-bis(aryl)-quinoxaline-6-carboxylic acid (1a, 1b, and 2) in solution and solid state. These compounds were fluorescent in solid films and in solutions with emission bands ranging from blue to green (445–517 nm). They showed a positive solvatochromism in the PL spectra, indicative of intramolecular charge transfer (ICT) in the excited state. 1a, 1b, and 2 exhibited Aggregation-Induced Enhanced Emission (AIEE) characteristics with a drastic change in properties by increasing alkyl chains and donor alkoxy groups. Their carboxylate potassium salts had a blueshift emission compared to the acid carboxylic form and a significant quenching in PL intensity in protic polar solvents. The salt of 1a presented an Aggregation-Induced Emission (AIE) profile, its weak fluorescence in water had an expressive enhancement by adding THF. Theoretical calculations were also carried out considering implicit solvent effects. The optimized structures of compounds and their simulated UV–vis absorption spectra showed no significant differences in water and acetonitrile. These results are in good agreement with the solvatochromism experiments. The calculated HOMO-LUMO energy gaps were 3.47 eV in both solvents, and the energy levels for HOMO and LUMO are slightly lower in water.

Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.

Over 30 compounds, including para-, meta-, and ortho-phenylenediboronic acids, ortho-substituted phenylboronic acids, benzenetriboronic acids, di- and triboronated thiophenes, and pyridine derivatives were investigated as potential β-lactamase inhibitors. The highest activity against KPC-type carbapenemases was found for ortho-phenylenediboronic acid 3a, which at the concentration of 8/4 mg/L reduced carbapenems' MICs up to 16/8-fold, respectively. Checkerboard assays revealed strong synergy between carbapenems and 3a with the fractional inhibitory concentrations indices of 0.1-0.32. The nitrocefin hydrolysis test and the whole cell assay with E. coli DH5α transformant carrying blaKPC-3 proved KPC enzyme being its molecular target. para-Phenylenediboronic acids efficiently potentiated carbapenems against KPC-producers and ceftazidime against AmpC-producers, whereas meta-phenylenediboronic acids enhanced only ceftazidime activity against the latter ones. Finally, the statistical analysis confirmed that ortho-phenylenediboronic acids act synergistically with carbapenems significantly stronger than other groups. Since the obtained phenylenediboronic compounds are not toxic to MRC-5 human fibroblasts at the tested concentrations, they can be considered promising scaffolds for the future development of novel KPC/AmpC inhibitors. The complexation of KPC-2 with the most representative isomeric phenylenediboronic acids 1a, 2a, and 3a was modeled by quantum mechanics/molecular mechanics calculations. Compound 3a reached the most effective configuration enabling covalent binding to the catalytic Ser70 residue.

Novel Acrylate-Based Derivatives: Design, Synthesis, Antiproliferative Screening, and Docking Study as Potential Combretastatin Analogues.

A variety of 3-(4-chlorophenyl) acrylic acids 4a,b and 3-(4-chlorophenyl)acrylate esters 5a-i were synthesized and structurally proven by spectroscopic studies such as IR, 1H NMR, and 13C NMR as well as mass spectrometry. All substances were investigated for their antiproliferative efficacy against the MDA-MB-231 cell line. Among these, acrylic acid compound 4b demonstrated the most potent cytotoxic effect with an IC50 value of 3.24 ± 0.13 μM, as compared to CA-4 (IC50 = 1.27 ± 09 μM). Additionally, acrylic acid molecule 4b displayed an inhibitory effect against β-tubulin polymerization with a percentage inhibition of 80.07%. Furthermore, compound 4b was found to produce considerable cell cycle arrest at the G2/M stage and cellular death, as demonstrated by FACS analysis. In addition, the in vivo antitumor screening of the sodium salt of acrylic acid 4b was carried out, and the results have shown that the tested molecule showed a significant decrease in viable EAC count and EAC volume, accompanied by a considerable increase in the life span prolongation, if compared to the positive control group. Furthermore, molecular modeling studies were performed to understand how the highly efficient chemicals 4b and 5e interact with the colchicine-binding region on tubulin. This work aims to shed light on the reasons behind their exceptional cytotoxicity and their better capacity to inhibit tubulin in comparison to CA-4.

(E)-6-Hydroxy-2-oxo-2H-chromen-7-yl 3-(4-hydroxy-3-methoxyphenyl)acrylate

A hybrid compound 5: (E)-6-hydroxy-2-oxo-2H-chromen-7-yl 3-(4-hydroxy-3-methoxyphenyl)acrylate composed of (E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid (ferulic acid) 1 and 6,7-hydroxycoumarin (esculetin) 3 was prepared in a 61% yield by the esterification reaction of protected ferulic acid 2a with esculetin 3 in the presence of triethylamine in dichloromethane for 3 h, followed by deprotection using 3M HCl. The structure of compound 5 was confirmed by 1H, 13C NMR spectroscopy, mass-spectrometry and elemental analysis.

3-Hydroxybutyrate-containing triterpenoid saponins from Brachyscome angustifolia and their immunogenic activity

Three unique hydroxybutyrate-containing triterpenoid saponins, angustiside A–C (1–3), were isolated from the shoots of Brachyscome angustifolia (Asteraceae). The extensive spectroscopic study showed that their aglycone is a previously undescribed one, 16-hydroxy olean-18-en-28-oic acid, named as angustic acid (1a), and 2 and 3 contain hydroxybutyrate moiety in their side chains. The absolute configuration of 1a was determined to be (3R,5R,9R,13S,16S) by X-ray crystallography. The immunity assay revealed that 2 and 3 containing both acyl chains and branched saccharides significantly enhanced the proliferation of OT-I CD8+ T cells and secretion of interferon gamma (IFN-γ), presenting their immunogenic activity.

Semisynthesis, Biological Evaluation and Molecular Docking Studies of Barbatic Acid Derivatives as Novel Diuretic Candidates.

Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid (6a-q') were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 μmol/L in vitro. All target compounds were characterized using 1H NMR, 13C NMR, and HRMS, and the spatial structure of compound 6w was confirmed using X-ray crystallography. The biological results showed that some derivatives, including 6c, 6b', and 6f', exhibited potent diuretic activity, and 6j and 6m displayed promising litholytic activity. Molecular docking studies further suggested that 6b' had an optimal binding affinity to WNK1 kinases related to diuresis, while 6j could bind to the bicarbonate transporter CaSR through a variety of forces. These findings indicate that some barbatic acid derivatives could be further developed into novel diuretic agents.

Dissipative Systems Driven by the Decarboxylation of Activated Carboxylic Acids.

ConspectusThe achievement of artificial systems capable of being maintained in out-of-equilibrium states featuring functional properties is a main goal of current chemical research. Absorption of electromagnetic radiation or consumption of a chemical species (a "chemical fuel") are the two strategies typically employed to reach such out-of-equilibrium states, which have to persist as long as one of the above stimuli is present. For this reason such systems are often referred to as "dissipative systems". In the simplest scheme, the dissipative system is initially found in a resting, equilibrium state. The addition of a chemical fuel causes the system to shift to an out-of-equilibrium state. When the fuel is exhausted, the system reverts to the initial, equilibrium state. Thus, from a mechanistic standpoint, the dissipative system turns out to be a catalyst for the fuel consumption. It has to be noted that, although very simple, this scheme implies the chance to temporally control the dissipative system. In principle, modulating the nature and/or the amount of the chemical fuel added, one can have full control of the time spent by the system in the out-of-equilibrium state.In 2016, we found that 2-cyano-2-phenylpropanoic acid (1a), whose decarboxylation proceeds smoothly under mild basic conditions, could be used as a chemical fuel to drive the back and forth motion of a catenane-based molecular switch. The acid donates a proton to the catenane that passes from the neutral state A to the transient protonated state B. Decarboxylation of the resulting carboxylate (1acb), generates a carbanion, which, being a strong base, retakes the proton from the protonated catenane that, consequently, returns to the initial state A. The larger the amount of the added fuel, the longer the time spent by the catenane in the transient, out-of-equilibrium state. Since then, acid 1a and other activated carboxylic acids (ACAs) have been used to drive the operation of a large number of dissipative systems based on the acid-base reaction, from molecular machines to host-guest systems, from catalysts to smart materials, and so on. This Account illustrates such systems with the purpose to show the wide applicability of ACAs as chemical fuels. This generality is due to the simplicity of the idea underlying the operation principle of ACAs, which always translates into simple experimental requirements.

An efficient synthesis of new 3,5‐bis(2‐arylthiazol‐4‐yl)‐1,2,4‐oxadiazole derivatives and their antimicrobial evaluation

AbstractA new series of 3,5‐bis(2‐arylthiazol‐4‐yl)‐1,2,4‐oxadiazole (8a–o) has been synthesized by modified reaction conditions. The reaction of ester 7a with N′‐hydroxy‐2‐phenylthiazole‐4‐carboximidamide 6a using NaOH in DMSO gave the formation of product 8a up to 40% yield. In the second method, the reaction with K2CO3 in toluene at reflux conditions gave a 50% yield. In the third method, the reaction condition was modified. The ester 7a was hydrolyzed to acid 9a. The reactions of acid 9a using N,N‐dimethyl amino pyridine (DMAP) in N,N‐dimethylformamide (DMF), followed by the addition of N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide hydrochloride (EDC·HCl), and then N′‐hydroxy‐2‐phenylthiazole‐4‐carboximidamide 6a, furnished a 65% yield of 8a. The compounds 8b–o were synthesized using DMAP and EDC·HCl as coupling reagents and gave 60%–72% yields. The structure of newly synthesized compounds was confirmed by spectral analysis. The synthesized compounds were screened for in vitro antimicrobial activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), Bacillus subtilis (NCIM2063), Staphylococcus albus (NCIM 2178), Candida albicans (NCIM 3100), and Aspergillus niger (ATCC 504). Among the 8a–o derivatives, eight compounds 8c, 8e, 8f, 8g, 8i, 8j, 8k, and 8l showed good activity S. albus with a MIC 31.25–62.5 μg/mL.

Synthesis, Structural Investigations, DFT Calculations, and Molecular Docking Studies of Novel 2-(Substituted-Aryloxymethyl)-5-(Pyridin-4-yl)-1, 3, 4-Oxadiazoles: Highly Potential InhA and Cytochrome c Peroxidase Inhibitors

We report derivatives of 2,5-disubstituted-1,3,4-oxadiazole as powerful anti-TB and antioxidant compounds. Using substituted aryloxy acetic acids (2a–f) and isoniazid (3) in the presence of phosphorus oxychloride, a series of new 2-(substituted-aryloxymethyl)-5-(pyridin-4-yl)-1,3,4-oxadiazoles (4a–f) are synthesized. IR, 1H NMR, and mass spectral data were used to physically and spectroscopically describe the synthesized molecules. Density Functional Theory (DFT) calculations were performed at the DFT/B3LYP level using 6-31 G++ (d, p) to reproduce the structure and geometry. The non-linear visual characteristic of compounds is determined by the first-order hyperpolarizability calculation. To analyze the charge transfer interface between the structures, HOMO and LUMO investigations were used. The in vitro anti-TB and antioxidant activity was carried out. The compound 4d exhibited excellent anti-TB activity with a MIC value of 3.12 µg/ml. The compounds 4b and 4c showed promising antioxidant activity at a concentration of 10 µg/ml with inhibition rates of 68.36% and 69.26% respectively. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK) and Cytochrome c peroxidase (2X08). All the compounds showed a strong binding affinity for the docked proteins.

Aniline Sulfonic Acid Induced Uniform Perovskite Film for Large‐Scale Photovoltaics

AbstractUnreacted/excess lead iodide is considered to be the archcriminal for the rapid degradation of hybrid perovskite solar cells. Meanwhile, a high‐quality perovskite film with uniform and large grain size is the basis for high‐performance perovskite modules. Herein, a dual‐site molecular additive 4‐Aniline Sulfonic Acid (4A) is developed to regulate the unreacted/excess PbI2 and passivate defects through hydrogen bonding and intermolecular interactions between amino, and a sulfate groups and PbI2, respectively. Furthermore, the introduction of the 4A additive can induce perovskite seeds to grow uniformly on the substrate, yielding dense, uniform and defect‐less perovskite films with large grain sizes. This enables the fabrication of perovskite photovoltaics with a maximum power conversion efficiency of 24.09% (0.09 cm2) and 20.87% (16 cm2), respectively. This work demonstrated a new strategy to deposit high‐quality large‐scale perovskite films for photovoltaic modules.