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1.
Heliyon ; 10(13): e33160, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39035494

ABSTRACT

In the present work, two hybrid series of pyrazole-clubbed pyrimidine and pyrazole-clubbed thiazole compounds 3-21 from 4-acetyl-1,3-diphenyl-1H-pyrazole-5(4H)-ole 1 were synthesized as novel antimicrobial agents. Their chemical structures were thoroughly elucidated in terms of spectral analyses such as IR, 1H NMR, 13C NMR and mass spectra. The compounds were in vitro evaluated for their antimicrobial efficiency against various standard pathogen strains, gram -ive bacteria (Pseudomonas aeruginosa, Klebsiella pneumonia), gram + ive bacteria (MRSA, Bacillus subtilis), and Unicellular fungi (Candida albicans) microorganisms. The ZOI results exhibited that most of the tested molecules exhibited inhibition potency from moderate to high. Where compounds 7, 8, 12, 13 and 19 represented the highest inhibition potency against most of the tested pathogenic microbes comparing with the standard drugs. In addition, the MIC results showed that the most potent molecules 7, 8, 12, 13 and 19 showed inhibition effect against most of the tested microbes at low concentration. Moreover, the docking approach of the newly synthesized compounds against DNA gyrase enzyme was performed to go deeper into their molecular mechanism of antimicrobial efficacy. Further, computational investigations to calculate the pharmacokinetics parameters of the compounds were performed. Among them 7, 8, 12, 13 and 19 are the most potent compounds revealed the highest inhibition efficacy against most of the tested pathogenic microbes comparing with the standard drugs.

2.
Bioorg Chem ; 148: 107401, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749115

ABSTRACT

New thienopyrimidine derivatives 2-16 have been synthesized and their in vitro cytotoxicity was evaluated against five different human cancer cell lines HCT-116, Hela, MDA-MB-231, MCF7 and PC3. Compounds 6e, 7a, 7b, 7d, 10c and 10e displayed the highest antitumor activity against all tested cell lines compared to Doxorubicin. Enzyme inhibition assay revealed that compounds 6e and 10e showed high inhibitory activity against EGFR-TK, with IC50 values of 0.133 and 0.151 µM, compared to Olmutinib (IC50 = 0.028 µM); while the highest DHFR inhibitory activity was shown by compounds 7d and 10e with IC50 values of 0.462 and 0.541 µM, compared to Methotrexate (IC50 = 0.117 µM). Cell cycle analysis following a flow cytometric study using colorectal HCT-116 cancer cell line proved that compound 6e induced cell cycle arrest in G0-G1 phase, while compound 10e arrested the cell cycle at both G0-G1 and S phases. Additionally, both compounds (6e and 10e) were potently able to induce apoptosis in HCT-116 cell line. Docking results of compounds 6e and 10e into the pocket of EGFR active site showed their similar main binding features with Olmutinib, while compounds 7d and 10e showed only moderate fitting into DHFR compared to methotrexate. In silico studies revealed that most of the tested compounds obeyed Lipinski's RO5 and showed positive drug likeness scores.


Subject(s)
Antineoplastic Agents , Cell Proliferation , Drug Screening Assays, Antitumor , ErbB Receptors , Folic Acid Antagonists , Molecular Docking Simulation , Pyrimidines , Tetrahydrofolate Dehydrogenase , Humans , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Tetrahydrofolate Dehydrogenase/metabolism , Folic Acid Antagonists/pharmacology , Folic Acid Antagonists/chemical synthesis , Folic Acid Antagonists/chemistry , Structure-Activity Relationship , Cell Proliferation/drug effects , Molecular Structure , Apoptosis/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry
4.
Clin Ophthalmol ; 17: 3719-3728, 2023.
Article in English | MEDLINE | ID: mdl-38084208

ABSTRACT

Objective: Silicone oils have the role in maintaining the attachment of the retina in conditions where the risk of retinal re-detachment is high. However, silicone oils have the tendency to emulsify with subsequent complications. In this work, analyses have been performed to understand changes that occurred to the optical, and physical characteristics of the oil after removal from the vitreous cavity of patients underwent pars plana vitrectomy (PPV) for fibrovascular membranes/tractional retinal detachment (FVM/TRD). Methods: Four samples of silicone oil were allocated from patients who underwent PPV for FVM/TRD. The Fourier-transform infrared (FTIR) spectroscopy, micro-viscometry, and ultraviolet-visible spectrometer analyses were utilized to determine the changes in its chemical bondings, viscosity, absorbance, transmittance, buoyance, and specific gravity. Results: The mean age of the patients was 49.0 years. The mean duration of silicone oil implantation was 18.9 months. FTIR analysis showed significant breaking in the chemical bonding that was related to the lens status during the primary PPV, the presence of significant retinal hemorrhages, the duration of silicone oil implantation, and the degree of silicone oil filling. Similarly, viscosity and contact angle analyses revealed a reduction in the viscosity with similar factors to the FTIR analysis. Moreover, absorbance and transmittance were largely affected by the aggressiveness of FVM/TRD. Conclusion: This study revealed that certain factors such as the age of the patient, duration of silicone oil implantation, lens status, and the presence of retinal hemorrhages, the degree of silicone oil filling and aggressiveness of FVM/TRD may contribute to the emulsification process.

5.
Molecules ; 28(22)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38005213

ABSTRACT

In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative 3. The as-prepared carbodithioate derivative 3 is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (4-9) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine-pyrimidine hybrid molecule (10). The latter was submitted to react with hydrazine monohydrate to provide the corresponding hydrazide derivative (11) which, under reaction with ethyl acetoacetate in refluxing ethanol containing catalytic amount of acetic acid, afforded the corresponding derivative (12). The structure of the newly synthesized compounds was affirmed by their spectral and microanalytical data. We also screened for their antimicrobial potential (ZOI and MIC) and conducted a kinetic study. Additionally, the mechanism of biological action was assessed by a membrane leakage assay and SEM imaging technique. Moreover, the biological activities and the binding modes of these compounds were further supplemented by an in silico docking study against E. coli ß-carbonic anhydrase. The amount of cellular protein released by E. coli is directly correlated to the concentration of compound 9, which was found to be 177.99 µg/mL following treatment with 1.0 mg/mL of compound 9. This finding supports compound 9's antibacterial properties and explains how the formation of holes in the E. coli cell membrane results in the release of proteins from the cytoplasm. The newly synthesized compounds represent acceptable antimicrobial activities with potential action against E. coli ß-carbonic anhydrase. The docking studies and antimicrobial activity test proved that compound (9) declared a greater activity than the other synthesized compounds.


Subject(s)
Anti-Infective Agents , Carbonic Anhydrases , Escherichia coli , Antipyrine , Anti-Infective Agents/pharmacology , Molecular Docking Simulation , Structure-Activity Relationship , Molecular Structure , Carbonic Anhydrase Inhibitors/pharmacology
6.
Plant Cell ; 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37824826

ABSTRACT

Model species continue to underpin groundbreaking plant science research. At the same time, the phylogenetic resolution of the land plant Tree of Life continues to improve. The intersection of these two research paths creates a unique opportunity to further extend the usefulness of model species across larger taxonomic groups. Here we promote the utility of the Arabidopsis thaliana model species, especially the ability to connect its genetic and functional resources, to species across the entire Brassicales order. We focus on the utility of using genomics and phylogenomics to bridge the evolution and diversification of several traits across the Brassicales to the resources in Arabidopsis, thereby extending scope from a model species by establishing a "model clade". These Brassicales-wide traits are discussed in the context of both the model species Arabidopsis thaliana and the family Brassicaceae. We promote the utility of such a "model clade" and make suggestions for building global networks to support future studies in the model order Brassicales.

7.
Curr Biol ; 33(19): 4052-4068.e6, 2023 10 09.
Article in English | MEDLINE | ID: mdl-37659415

ABSTRACT

The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Brassicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To evaluate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moderate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.


Subject(s)
Arabidopsis , Brassicaceae , Phylogeny , Brassicaceae/genetics , Arabidopsis/genetics , Biodiversity
8.
ACS Omega ; 8(26): 23901-23912, 2023 Jul 04.
Article in English | MEDLINE | ID: mdl-37426276

ABSTRACT

In this study, a novel heterogeneous catalyst (Fe3O4@ß-CD@Pd) has been developed by the deposition of palladium nanoparticles on the ß-cyclodextrin-functionalized surface of magnetic Fe3O4. The catalyst was prepared by a simple chemical co-precipitation method and characterized extensively by using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-optical emission spectrometry (ICP-OES) analyses. Herein, the applicability of the prepared material was evaluated for the catalytic reduction of environmentally toxic nitroarenes to the corresponding anilines. The catalyst Fe3O4@ß-CD@Pd showed excellent efficiency for the reduction of nitroarenes in water under mild conditions. A low catalyst loading of 0.3 mol % Pd is found to be efficient for reducing nitroarenes in excellent to good (99-95%) yields along with high TON values (up to 330). Nevertheless, the catalyst was recycled and reused up to the 5th cycle of reduction of nitroarene without any loss of significant catalytic activity.

9.
PhytoKeys ; 220: 127-144, 2023.
Article in English | MEDLINE | ID: mdl-37251613

ABSTRACT

Based on recent achievements in phylogenetic studies of the Brassicaceae, a novel infrafamilial classification is proposed that includes major improvements at the subfamilial and supertribal levels. Herein, the family is subdivided into two subfamilies, Aethionemoideae (subfam. nov.) and Brassicoideae. The Brassicoideae, with 57 of the 58 tribes of Brassicaceae, are further partitioned into five supertribes, including the previously recognized Brassicodae and the newly established Arabodae, Camelinodae, Heliophilodae, and Hesperodae. Additional tribus-level contributions include descriptions of the newly recognized Arabidopsideae, Asperuginoideae, Hemilophieae, Schrenkielleae, and resurrection of the Chamireae and Subularieae. Further detailed comments on 17 tribes in need of clarifications are provided.

10.
ACS Omega ; 8(13): 11880-11888, 2023 Apr 04.
Article in English | MEDLINE | ID: mdl-37033858

ABSTRACT

This study describes the synthesis of graphene oxide-modified magnetite (rGO/Fe3O4) and its use as an electrochemical sensor for the quantitative detection of hemoglobin (Hb). rGO is characterized by a 2θ peak at 10.03° in its X-ray diffraction, 1353 and 1586 cm-1 vibrations in Raman spectroscopy, while scanning electron microscopy coupled with energy-dispersive spectroscopy of rGO and rGO/Fe3O4 revealed the presence of microplate structures in both materials and high presence of iron in rGO/Fe3O4 with 50 wt %. The modified graphite pencil electrode, GPE/rGO/Fe3O4, is characterized using cyclic voltammetry. Higher electrochemical surface area is obtained when the GPE is modified with rGO/Fe3O4. Linear scan voltammetry is used to quantify Hb at the surface of the sensor using ferrocene (FC) as an electrochemical amplifier. Linear response for Hb is obtained in the 0.1-1.8 µM range with a regression coefficient of 0.995, a lower limit of detection of 0.090 µM, and a limit of quantitation of 0.28 µM. The sensor was free from interferents and successfully used to sense Hb in human urine. Due to the above-stated qualities, the GPE/rGO/Fe3O4 electrode could be a potential competitive sensor for trace quantities of Hb in physiological media.

11.
Nanomaterials (Basel) ; 13(7)2023 Mar 28.
Article in English | MEDLINE | ID: mdl-37049294

ABSTRACT

We fabricated ferroelectric films of the organic molecular diisopropylammonium chloride (DIPAC) using the dip-coating technique and characterized their properties using various methods. Fourier-transform infrared, scanning electron microscopy, and X-ray diffraction analysis revealed the structural features of the films. We also performed ab-initio calculations to investigate the electronic and polar properties of the DIPAC crystal, which were found to be consistent with the experimental results. In particular, the optical band gap of the DIPAC crystal was estimated to be around 4.5 eV from the band structure total density-of-states obtained by HSE06 hybrid functional methods, in good agreement with the value derived from the Tauc plot analysis (4.05 ± 0.16 eV). The films displayed an island-like morphology on the surface and showed increasing electrical conductivity with temperature, with a calculated thermal activation energy of 2.24 ± 0.03 eV. Our findings suggest that DIPAC films could be a promising alternative to lead-based perovskites for various applications such as piezoelectric devices, optoelectronics, sensors, data storage, and microelectromechanical systems.

12.
J Fluoresc ; 33(6): 2349-2360, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37058190

ABSTRACT

The furo[2,3-b]pyridine moiety is an important scaffold for many biologically active compounds, therefore, the spectral data of the derivative 1-(3-Amino-6-(2,5-dichlorothiophen-3-yl)-4-phenylfuro[2,3-b]pyridin-2-yl) ethenone (FP1) were investigated. Analysis of absorption-pH profile and Förster cycle of FP1 revealed that its excited state is more acidic than its ground state ([Formula: see text] < [Formula: see text]). The main fluorescence emission band of FP1 at 480 nm (in hexane) is shifted to longer wavelengths with increasing polarities of solvents. Linear Lippert's plot and linear correlation between bands maxima and Camlet-Taft parameter, α, of the protic solvents indicated efficient intramolecular charge transfer and noticeable H-bonding. Moreover, the disappearance of the absorption band of FP1 at 385 nm in water, along with the noticeable red shift and quenching of the emission band, and the lower lifetime, relative to nonaqueous solvents, indicate the interruption of the furo[2,3-b]pyridine aromatic moiety. In addition, results from the Time Dependent Density Functional Theory (TDDFT) and Molecular Mechanic (MM) calculations were in agreement with experimentally determined spectra of FP1.

13.
J Enzyme Inhib Med Chem ; 38(1): 2189578, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36919632

ABSTRACT

The dual c-Met/vascular endothelial growth factor receptor 2 (VEGFR-2) TK inhibition is a good strategy to overcome therapeutic resistance to small molecules VEGFR-2 inhibitors. In this study, we designed 3-substituted quinazoline-2,4(1H,3H)-dione derivatives as dual c-Met/VEGFR-2 TK inhibitors. We introduced new synthetic methods for reported derivatives of 3-substituted quinazoline-2,4(1H,3H)-dione 2a-g, in addition to the preparation of some new derivatives namely, 3 and 4a-j. Three compounds namely, 2c, 4b, and 4e showed substantial amount of inhibition for both c-Met and VEGFR-2 TK (IC50 range 0.052-0.084 µM). Both compounds 4b, 4e showed HB with highly conserved residue Asp1222 in the HB region of c-Met TK. For VEGFR-2 TK, compound 4b showed HB with a highly conserved residue Asp1046 in the HB region. Compound 4e showed HB with Glu885 and Asp1046. Moreover, in silico prediction of pharmacokinetic and physicochemical parameters of target compounds was carried out using SwissADME website. The quinazoline-2,4(1H,3H)-dione derivatives are promising antiproliferative candidates that require further optimisation.HighlightsNew 3-substituted quinazoline-2,4(1H,3H)-dione derivatives were synthesised and characterised.Compounds 4b and 4e showed higher cytotoxic activity than cabozantinib against HCT-116 colorectal cell lines.Both compounds 4b and 4e showed less toxicity to WI38 normal cell line compared to HCT 116 colon cancer cell line.Compound 4b was superior to cabozantinib in VEGFR-2 inhibition while compound 2c was equipotent to cabozantinib.Compounds 4b and 4e showed remarkable c-Met inhibitory activity.Compounds 4b and 4e arrested cell cycle and induced significant levels of apoptosis.In silico ADME prediction revealed high oral bioavailability and enhanced water solubility of target compounds as compared to cabozantinib.Target compounds interacted with both c-Met and VEGFR-2 active site in similar way to cabozantinib.


Subject(s)
Antineoplastic Agents , Quinazolines , Humans , Structure-Activity Relationship , Quinazolines/pharmacology , Quinazolines/chemistry , Vascular Endothelial Growth Factor Receptor-2 , Vascular Endothelial Growth Factor A , Cell Proliferation , Antineoplastic Agents/chemistry , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Molecular Docking Simulation , Drug Screening Assays, Antitumor , Molecular Structure , Drug Design
14.
Mol Ecol ; 32(2): 492-503, 2023 01.
Article in English | MEDLINE | ID: mdl-36326301

ABSTRACT

Numerous high-elevation alpine plants of the Qinghai-Tibet Plateau (QTP) also have disjunct distribution in adjacent low-altitude mountains. The out-of-QTP versus into-the-QTP hypothesis of alpine plants provide strong evidence for the highly disputed assumption of the massive ice sheet developed in the central plateau during the Last Glacial Maximum (LGM). In this study, we sequenced the genomes of most known populations of Megadenia, a monospecific alpine genus of Brassicaceae distributed primarily in the QTP, though rarely found in adjacent low-elevation mountains of north China and Russia (NC-R). All sequenced samples clustered into four geographic genetic groups: one pair was in the QTP and another was in NC-R. The latter pair is nested within the former, and these findings support the out-of-QTP hypothesis. Dating the four genetic groups and niche distribution suggested that Megadenia migrated out of the QTP to adjacent regions during the LGM. The NC-R group showed a decrease in the effective population sizes. In addition, the genes with high genetic divergences in the QTP group were mainly involved in habitat adaptations during low-altitude colonization. These findings reject the hypothesis of development massive ice sheets, and support glacial survival of alpine plants within, as well as further migration out of, the QTP.


Subject(s)
Brassicaceae , Tibet , Brassicaceae/genetics , China , Ecosystem , Plants , Genomics
15.
J Ocul Pharmacol Ther ; 38(10): 717-727, 2022 12.
Article in English | MEDLINE | ID: mdl-36318488

ABSTRACT

Purpose: Silicone oil (SO) is a crucial tool in vitreoretinal surgery. SO has the tendency to emulsify depending on certain factors. In this work, detailed analyses have been conducted to understand changes that occurred to the physical, optical, and chemical characteristics of the oil after removal from the vitreous cavity. Methods: Five samples of SO were collected from patients who underwent vitrectomy for rhegmatogenous retinal detachment. The fourier-transform infrared (FTIR) spectroscopy, ultraviolet-visible spectrometer, and contact angle analysis were utilized to determine the changes in its chemical bondings, transmittance, absorbance, viscosity, buoyance, and specific gravity. Results: FTIR analysis showed significant changes in the chemical bonding that might be related to the age of the patient, lens status, the presence of retinal hemorrhages, and the exposure to laser after implantation of SO. In addition, contact angle analysis revealed that the viscosity might be affected by duration of implantation and the age of the patient. Moreover, transmittance and absorbance were largely affected by the exposure to laser retinopexy after implantation. Conclusion: This study showed that certain factors such as the age of the patient, the exposure to laser, lens status, and the presence of retinal hemorrhages may contribute to the emulsification process.


Subject(s)
Retinal Detachment , Silicone Oils , Humans , Retinal Detachment/surgery , Retinal Hemorrhage
17.
Sci Rep ; 12(1): 16246, 2022 09 28.
Article in English | MEDLINE | ID: mdl-36171229

ABSTRACT

Many benzoxazole-based and similar scaffolds were reported to have wide-range of anticancer activities. In this study, four series of benzoxazole derivatives were designed by combining benzoxazole scaffold with different amines via a reversed phenyl amide linker to produce the compounds of series A, B and C. A fourth new hybrid of benzoxazole with 1,2,3 triazole ring (series D) was also designed. The designed compounds were synthesized and screened for their anti-breast cancer activity against MDA-MB-231 and MCF-7 cell lines using MTT assay. The most potent cytotoxic compounds; 11-14, 21, 22, 25-27 were further evaluated for their in vitro PARP-2 enzyme inhibition. Compounds 12 and 27 proved to be the most active PARP-2 inhibitors with IC50 values of 0.07 and 0.057 µM, respectively. Compounds 12 and 27 caused cell cycle arrest in mutant MCF-7 cell line at G2/M and G1/S phase, respectively and they possessed significant apoptosis-promoting activity. Docking results of compounds 12 and 27 into PARP-2 pocket demonstrated binding interactions comparable to those of olaparib. Their predicted pharmacokinetic parameters and oral bioavailability appeared to be appropriate. Collectively, it could be concluded that compounds 12 and 27 are promising anti-breast cancer agents that act as PARP-2 inhibitors with potent apoptotic activity.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Amides/pharmacology , Amines/pharmacology , Antineoplastic Agents/chemistry , Benzoxazoles/chemistry , Benzoxazoles/pharmacology , Breast Neoplasms/drug therapy , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Female , Humans , Molecular Docking Simulation , Molecular Structure , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Structure-Activity Relationship , Triazoles/pharmacology
18.
ACS Omega ; 7(29): 25265-25277, 2022 Jul 26.
Article in English | MEDLINE | ID: mdl-35910116

ABSTRACT

A series of novel pyrazolinone chalcones 3-9 have been synthesized through the condensation of azo pyrazolinone derivatives with various aromatic aldehydes. Spectroscopic techniques and elemental analysis have both corroborated this. Furthermore, all compounds were screened in silico for their ability to inhibit cancer proliferation and metastasis by targeting the PI3K/Akt signaling pathway. This inhibitory pathway might be an efficient approach for the death of cancer cells, angiogenesis, and metastasis prevention. Our results indicated that only compound 6b was the top-ranked. It demonstrated the highest binding energies of -11.1 and -10.7 kcal/mol against the target proteins PI3K and Akt, respectively; thus, it was chosen for in vitro studies. Compound 6b exhibited the most effective cytotoxic impact against the Caco cell line with IC50 of 23.34 ± 0.14 µM. Furthermore, it showed significant inhibition of PI3K/Akt proteins and oxidative stress, leading to elevated Bax and p53 expression, reduced Bcl-2 expression, and triggered cell cycle arrest at the sub-G0/G1 phase. Additionally, it showed significant downregulation of the Raf-1 gene, leading to ERK1/2 protein inhibition. These findings demonstrate that compound 6b obeyed Lipinski's rule of five and might be used as a favored scaffold for cancer treatment by inhibiting proliferation and metastasis via inhibition of the PI3K/Akt and Raf-1/ERK1/2 signaling pathways.

19.
Molecules ; 27(11)2022 Jun 04.
Article in English | MEDLINE | ID: mdl-35684551

ABSTRACT

Novel 1,3,4-thiadiazole derivatives were synthesized through the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate and the appropriate hydrazonoyl halides in the presence of a few drops of diisopropylethylamine. The chemical structure of the newly fabricated compounds was inferred from their microanalytical and spectral data. With the increase in microbial diseases, fungi remain a devastating threat to human health because of the resistance of microorganisms to antifungal drugs. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) have higher mortality rates in many populations. The present study aimed to find new antifungal agents using the disc diffusion method, and minimal inhibitory concentration (MIC) values were estimated by the microdilution assay. An in vitro experiment of six synthesized chemical compounds exhibited antifungal activity against Rhizopus oryzae; compounds with an imidazole moiety, such as the compound 7, were documented to have energetic antibacterial, antifungal properties. As a result of these findings, this research suggests that the synthesized compounds could be an excellent choice for controlling black fungus diseases. Furthermore, a molecular docking study was achieved on the synthesized compounds, of which compounds 2, 6, and 7 showed the best interactions with the selected protein targets.


Subject(s)
Anti-Infective Agents , COVID-19 , Thiadiazoles , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Bacteria , Fungi , Humans , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Structure-Activity Relationship , Thiadiazoles/chemistry , Thiadiazoles/pharmacology
20.
Plant Physiol ; 190(1): 403-420, 2022 08 29.
Article in English | MEDLINE | ID: mdl-35670733

ABSTRACT

Angiosperm genome evolution was marked by many clade-specific whole-genome duplication events. The Microlepidieae is one of the monophyletic clades in the mustard family (Brassicaceae) formed after an ancient allotetraploidization. Postpolyploid cladogenesis has resulted in the extant c. 17 genera and 60 species endemic to Australia and New Zealand (10 species). As postpolyploid genome diploidization is a trial-and-error process under natural selection, it may proceed with different intensity and be associated with speciation events. In Microlepidieae, different extents of homoeologous recombination between the two parental subgenomes generated clades marked by slow ("cold") versus fast ("hot") genome diploidization. To gain a deeper understanding of postpolyploid genome evolution in Microlepidieae, we analyzed phylogenetic relationships in this tribe using complete chloroplast sequences, entire 35S rDNA units, and abundant repetitive sequences. The four recovered intra-tribal clades mirror the varied diploidization of Microlepidieae genomes, suggesting that the intrinsic genomic features underlying the extent of diploidization are shared among genera and species within one clade. Nevertheless, even congeneric species may exert considerable morphological disparity (e.g. in fruit shape), whereas some species within different clades experience extensive morphological convergence despite the different pace of their genome diploidization. We showed that faster genome diploidization is positively associated with mean morphological disparity and evolution of chloroplast genes (plastid-nuclear genome coevolution). Higher speciation rates in perennials than in annual species were observed. Altogether, our results confirm the potential of Microlepidieae as a promising subject for the analysis of postpolyploid genome diploidization in Brassicaceae.


Subject(s)
Brassicaceae , Genome, Plastid , Brassicaceae/genetics , Evolution, Molecular , Genetic Speciation , Genome, Plastid/genetics , Phylogeny , Plastids/genetics
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