Design, synthesis, and anticancer evaluation of novel coumarin/thiazole congeners as potential CDK2 inhibitors with molecular dynamics.

A series of novel coumarin-thiazoles was designed and synthesized as a possible CDK2 inhibitor with anticancer activity with low toxicity. The design relied on having hydrazine thiazole or its open-form thioamide to form H-bonds with the ATP binding site while coumarin maintained the crucial hydrophobic interactions for proper fitting. The biological evaluation revealed that the hydroxycoumarin-thiazole derivative 6c demonstrated the best inhibition with HepG2 and HCT116 IC50 2.6 and 3.5 µM, respectively. Similarly, its open thioamide chain congener 5c exhibited potent inhibition on MCF-7 and HepG2 with IC50 of 4.5 and 5.4 µM, respectively. Molecular docking simulations supported the assumption of inhibiting CDK2 by preserving the crucial interaction pattern with the hinge ATP site and the surrounding hydrophobic (HPO) side chains. Furthermore, molecular dynamics simulations of 5c and 6c established satisfactory stability and affinity within the CDK2 active site.

Synthesis, characterization, and anticancer evaluation of novel 4-hydrazinothiazole analogs.

Single-step synthesis of novel 4-hydrazinothiazole derivatives 6a-e was achieved under mild conditions using the sequential four-components method involving isothiocyanate, aminoguanidine, carbonyl adduct, and α-haloketone derivatives. Deprotection of these hydrazinothiazoles was influenced by acylation, providing a novel group of diacylated molecular structures with a broader scope for the design of thiazolyl-containing drugs 7a and 7b. FTIR, 1 H/13 C NMR, LC-MS spectroscopy, and CHN elemental analyses were used to study the compound chemical structures. Using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on human periodontal ligament fibroblast (HPDLF) cells, the 4-hydrazinothiazole derivatives were screened for cytotoxicity in an in vitro cytotoxicity investigation. The 4-hydrazinothiazole compound 6b bearing an isopropylidene-hydrazino group demonstrated strongly potent cytotoxicity against CAKI1 (IC50  = 1.65 ± 0.24 µM) and A498 (IC50 of 0.85 ± 0.24 µM). Furthermore, the chloroacetyl-containing thiazole compound 7a displayed efficient inhibition of growth against the test cell lines CAKI1 and A498 at low micromolar concentrations, IC50 0.78 and 0.74 µM, respectively.

Facile preparation of smart nanocomposite adhesive with superhydrophobicity and photoluminescence.

Smart photoluminescent nanocomposite adhesive was developed toward simple commercial manufacturing of long-persistent luminescent and hydrophobic applications. The prepared photoluminescent glue was able to continue emitting light after turning the illumination source off even after being in the dark for up to 1.5 h. Lanthanide-doped strontium aluminum oxide (LSAO) nanoparticles (NPs) dispersed in liquid silicone rubber (SR) was prepared to function as nanocomposite glue for various surfaces. Using nano-scaled particles, LSAO was uniformly disseminated without agglomeration in the silicone rubber matrix, enabling the produced nanocomposite glue to transmit light. For the applied glues, there is an excitation peak determined at 365 nm, and an emission peak determined at 518 nm. Depending on the LSAO ratio, the photoluminescence spectra displayed either afterglow phosphorescence or fluorescence. Photochromism was monitored from transparent to greenish under UV irradiation and greenish-yellow in darkness. The glued samples benefit from enhanced superhydrophobicity and scratch resistance due to LSAO NPs embedded in the silicone rubber matrix. The glueed LSAO@SR nanocomposite showed high durability and resistance to light damages. This research established the feasibility of mass-producing smart glue for various uses such as building safety directed signs and smart windows.

Microwave-assisted solvent-free synthesis of some novel thiazole-substituted thiosemicarbazone analogues: antimicrobial and anticancer studies.

The increased resistance to antibiotics has compelled researchers to devise novel active compounds targeting multidrug-resistant pathogenic microorganisms. A series of thiosemicarbazone derivatives was synthesized by reacting thiosemicarbazide with 2-aryl-4-formylthiazole, 2-aryl-5-formyl-4-methylthiazole, and/or 5-acetyl-2-aryl-4-methylthiazole compounds. These thiosemicarbazone-based thiazole adducts were evaluated for their inhibitory activities against tuberculosis H37Ra and Bovis BCG mycobacteria. Their cytotoxicity was assessed against two cancer cell lines: colonic carcinoma (HCT-116) and cervical cancer (HeLa). Notably, these thiosemicarbazones exhibited minimal cytotoxic effects on these cell lines even at their highest concentrations. Furthermore, the prepared thiosemicarbazone derivatives demonstrated significant antimicrobial efficacy against Bacillus subtilis and Staphylococcus aureus (Gram-positive bacterial pathogens) as well as Escherichia coli and Pseudomonas fluorescens (Gram-negative bacterial pathogens). While most of the prepared thiosemicarbazone derivatives exhibited moderate activity against Candida albicans (a fungal strain), their performance was notable. The thiosemicarbazone-based thiazole adducts were also successfully synthesized using a solvent-free approach under microwave irradiation. Compared with conventional reflux methods, the microwave-assisted technique yielded high thiazole yields within just 5 min, obviating the need for catalysis. This study signifies significant strides toward the rational design of more potent antimycobacterial agents.

Synthesis, antioxidant effectiveness, and docking study of new benzothiazolyl-chromenone-based fluorophores.

As chromenones demonstrate significant push-pull fluorescence effects on the development and description of novel push-pull fluorescent compounds based on chromenone with exceptional molar extinction coefficients, benzothiazolyl-chromenone-based fluorophores were created by refluxing ethanol/piperidine over Knoevenagel's condensation. Many spectral methods, including 1 H-NMR, FT-IR analysis, and (C, H, N) analysis, were used to demonstrate the molecular structures of the synthesized benzothiazolyl-chromenone-based fluorophores. The synthesized fluorophore UV-vis absorption and emission spectra showed significant extinction coefficients, which were observed to be influenced by the substituted benzothiazole bridge in conjugation with the alkoxy donor moiety. It was discovered that the alkoxyl group-bonded substituents had an effect on the maximum absorbance wavelength. The benzothiazolyl-chromenone hybrid achieved antioxidant efficacy that compared favourably with commonly used medications [butylated hydroxytoluene (BHT) and vitamin C]. In contrast with the other hybrids, hybrid 3c, which has a hexyloxy tail, made good claims about its suitable action towards vitamins and reference medications. Additionally, the synthesized benzothiazolyl-chromenone-based hybrids showed marked coordination with antioxidant efficacy when docked studies of the hybrids towards the chosen 3NM8 protein were conducted.

Synthesis and characterization of Cu(II)-pyrazole complexes for possible anticancer agents; conformational studies as well as compatible in-silico and in-vitro assays.

New pyrazole derivatives were prepared and used to synthesize new bioactive agents from Cu(II) complexes that have OSN donors. Analytical and spectral (IR, UV-Vis, MS, 1H NMR, ESR & XRD) instruments characterized these complexes as well as their corresponding ligands. The bonding mode has been modified from ligand to ligand and the molar ratio for isolated complexes has also varied (1:1/1:2, M:L). The geometry of isolated complexes was commonly proposed, based on electronic transitions and ESR spectral-parameters. Via computational approaches, these structures were optimized using standard programs (Gaussian 09 & HyperChem 8.1) under the required basis set. Consequently, important physical characteristics have been obtained after finishing the optimization process. Inhibition behavior of all new synthesizes was studied by MOE module as in-silico approach which conducted versus the crystal structure of NUDT5 protein (6gru) of breast cancer cells. The interaction features summarized from docking processes, reveal effective inhibition validity for new Cu(II) complexes versus breast cancer cells. This according to scoring energy values and the stability of docking complexes in true interaction path (bond length ≤3.5 Å) particularly with Cu(II)-L3 and Cu(II)-L4 complexes. This reflects the possibility of successful behavior during practical application through in-vitro assay that intended in this study. Finally, the degree of toxicity of such new compounds to the breast cancer cell line was determined by in-vitro screening. To judge perfectly on their toxicity, in-vitro screening must compared to positive control as Doxorubicin (reference drug). IC50 values were calculated and represent Cu(II) complexes as outstanding cytotoxic agents which revealed superiority on the reference drug itself.

Alpha-glucosidase and amylase inhibitory effects of Eruca vesicaria subsp. longirostris essential oils: synthesis of new 1,2,4-triazole-thiol derivatives and 1,3,4-thiadiazole with potential inhibitory activity.

Context: The substantial increase in the number of diabetics has encouraged the search for new pharmacological strategies to face this problem. In this regard, triazole and its derivatives have attracted considerable attention for the past few decades due to their pharmacological significance. Objective: Evaluation of the inhibitory activity of α-glucosidase and α-amylase in essential oils extracted from plant Eruca vesicaria (L) Cav. subsp. longirostris (Brassicaceae) (EVL) and to verify whether the triazoles and thiadiazol bearing the lipophilic 4-methylthiobutyl group synthesized from the essential oil contribute to this activity. Materials and methods: The essential oils were extracted by hydrodistillation from leaf, stem, root, and fruit of EVL, and their chemical compositions were analyzed by gas chromatography and gas chromatography-mass spectrometry. We present here the synthesis of three new types of 1,2,4-triazole-thiol and 1,3,4-thiadiazol and the structures were confirmed by NMR, mass spectrometry. The α-glucosidase and α-amylase inhibitory activities were investigated in vitro. Results: The main compound in fruit, stem, and root was erucin (96.6, 85.3, and 83.7%, respectively). The three essential oils of the fruit, stem, and root have strong inhibitory activity on α-glucosidase and α-amylase; IC50 values of roots were 0.81 ± 0.02 µg/mL and 0.13 ± 0.01 µg/mL, respectively. Derivatives 1 b, 2 b, 3 b, and 2c showed remarkable inhibitory activity against α-glucosidase with potencies better than that of acarbose with IC50 values ranging between 0.49 and 1.43 µM. Conclusions: Current results indicate that ECL fruit essential oil can be used as a natural precursor for the synthesis of triazoles as potential hypoglycemic agents.

Chemical Composition, Antibacterial, Antioxidant and in Vitro Antidiabetic Activities of Essential Oils from Eruca vesicaria.

This work describes the study of the chemical composition and bioactivity of the essential oils (EOs) of the different organs (leaves, flowers, stems and roots) from Eruca vesicaria. According to the GC and GC/MS analysis, all the EOs were dominated by erucin (4-methylthiobutyl isothiocyanate) with a percentage ranging from 17.9 % (leaves) to 98.5 % (roots). The isolated EOs were evaluated for their antioxidant (DPPH, ABTS and ß-carotene/linoleic acid), antibacterial and inhibitory property against α-amylase and α-glucosidase. Most EOs exhibited an interesting α-glucosidase and α-amylase inhibitory potential. The roots essential oil was found to be the most active with IC50 values of 0.80±0.06 and 0.11±0.01 µg mL-1 , respectively. The essential oil of roots exhibited the highest antioxidant activity (DPPH, PI=92.76±0.01 %; ABTS, PI=78.87±0.19; and ß-carotene, PI=56.1±0.01 %). The isolated oils were also tested for their antibacterial activity against two Gram-positive and three Gram-negative bacteria. Moderate results have been noted by comparison with Gentamicin used as positive control.

Synthesis and antimicrobial activity of some new pyrimidinone and oxazinone derivatives fused with thiophene rings using 2-chloro-6-ethoxy-4-acetylpyridine as starting material.

A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,ß-Unsaturated ketones 3a-c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones 4a-c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters 5a-c. The esters 5a-c were cyclized by action of sodium methoxide to aminoesters 6a-c, which were aminolyzed with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a-c were hydrolyzed with NaOH to the corresponding sodium salt 8a-c, which were treated with acetic anhydride to afford 2-methyloxazinones 9a-c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a-c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones 11a-c. The antimicrobial screening showed that many of these compounds have good antibacterial and antifungal activities comparable to streptomycin and fusidic acid used as reference drugs.

In situ synthesis, photometric and spectroscopic studies of chelating system during the 1,4,7,10,13,16-hexaoxacyclooctadecane charge transfer reaction with different acceptors.

Electron donor acceptor complexes (EDA) of the 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6) as a rich donor were spectrophotometrically discussed and synthesized in solid form according the interactions with different nine of usual π-acceptors like 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione (p-chloranil; p-CHL), tetrachloro-1,2-benzoquinone (o-chloranil; o-CHL), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), tetracyanoquinodimethane (TCNQ), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone (chloranilic acid; CLA), N-bromosuccinimide (NBS), 2,4,6-trinitrophenol (picric acid; PA). Spectroscopic and physical data such as formation constant (K(CT)), molar extinction coefficient (ɛ(CT)), standard free energy (ΔG°), oscillator strength (f), transition dipole moment (µ), resonance energy (R(N)) and ionization potential (I(p)) were estimated in chloroform or methanol at 25°C. Based on the elemental analysis and photometric titrations the CT-complexes were formed indicated the formation of 1:1 charge-transfer complexes for the o-CHL, TCNQ, DCQ, DBQ and NBS acceptors but 1:3 ratio for p-CHL, DDQ, CLA and PA, respectively. The charge-transfer interactions were interpretative according to the formation of dative ion pairs [18C6(•+), A(•-)], where A is acceptor. All of the resulting charge transfer complexes were isolated in amorphous form and the complexes formations on IR and (1)H NMR spectra were discussed.