Synthesis of Bis-thiazoles Tethered 1,4-Dihydropyridine and Pyridine Linkers via Simple Oxidation and their Molecular Docking as VEGFR -TK Inhibitors.

AIM: In this study, a neoteric and expedient oxidation method is applied for a variety of Hantzsch 1,4-dihydropyridine derivatives such as 1,4-dihydro- 2,6-dimethyl-3,5-diacetylpyridine, 3,5-bis-hydrazono--2,6-dimethyl-1,4-dihydropyridine, and 3,5-bis-thiazoly-2,6-dimethyl-1,4-dihydro pyridine. METHOD: This simple oxidation is based upon the in situ generation of nitrous acid from an aqueous sodium nitrite and acetic acid mixture and could be used to downgrade costs, sustain resources, and minimize chemical wastes. Also, a molecular modeling strategy was used to study the mechanism of action for various derivatives of bis-hydrazinylidene- thiazole as the protein Vascular Endothelial Growth Factor Receptor Tyrosine Kinase (VEGFR TK) inhibitor through evaluating their binding scores and modes compared with Sorafenib as a reference standard. RESULT: The results revealed that the interaction of hydrazinylidene and thiazole as an anticancer Tyrosine Kinase inhibitor has been improved. CONCLUSION: Additionally, the compounds exhibiting the highest activity were assessed for their potential anticancer effects against HepG-2, MCF-7, and WI-38 cells, and the outcomes demonstrated encouraging activity against cancer.

Novel maleic anhydride derivatives: liquid crystalline materials with enhanced mesomorphic and optical characteristics.

A new class of liquid crystalline materials, 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl 4-(alkoxy)benzoates (Mn), derived from maleic anhydride, was synthesized and studied for mesomorphic and optical properties. These materials consist of three derivatives with varying terminal flexible chain lengths (6-12 carbons) linked to the phenyl ring near the ester bond. The study employed differential scanning calorimetry and polarized optical microscopy (POM) to characterize the mesomorphic properties. Molecular structures were elucidated using elemental analysis, FT-IR, and NMR spectroscopy. The findings reveal that all the synthesized maleic anhydride derivatives exhibit enantiotropic nematic (N) mesophases. The insertion of the heterocyclic maleic anhydride moiety into the molecular structure influences the stability and range of the N phase. Additionally, entropy changes during N-isotropic transitions are of small magnitude and exhibit non-linear trends independent of the terminal alkoxy chain length (n). This suggests that the ester linkage group does not significantly promote molecular biaxiality, and the clearing temperature values are relatively high. By comparing the investigated materials with their furan derivatives found in existing literature, it was established that the substitution examined in this study induces the formation of nematic phases.

Synthesis, Biological Evaluation, and Molecular Docking of Novel Azolylhydrazonothiazoles as Potential Anticancer Agents.

A novel set of thiazolylhydrazonothiazoles bearing an indole moiety were synthesized by subjection reactions of carbothioamide derivative and hydrazonoyl chlorides (or α-haloketones). The cytotoxicity of the synthesized compounds was evaluated against the colon carcinoma cell line (HCT-116), liver carcinoma cell line (HepG2), and breast carcinoma cell line (MDA-MB-231), and demonstrated encouraging activity. Furthermore, when representative products were assessed for toxicity against normal cells, minimal toxic effects were observed, indicating their potential safety for use in pharmacological studies. The mechanism of action of the tested products, as inhibitors of the epidermal growth factor receptor tyrosine kinase domain (EGFR TK) protein, was suggested through docking studies that assessed their binding scores and modes, in comparison to a reference standard (W19), thus endorsing their anticancer activity.

Green Synthetic Approaches of 2-Hydrazonothiazol-4(5H)-ones Using Sustainable Barium Oxide-Chitosan Nanocomposite Catalyst.

The diverse applications of metal oxide-biopolymer matrix as a nanocomposite heterogenous catalyst have caused many researches to scrutinize the potential of this framework. In this study, a novel hybrid barium oxide-chitosan nanocomposite was synthesized through a facile and cost-effective co-precipitation method by doping barium oxide nanoparticles within the chitosan matrix at a weight percentage of 20 wt.% BaO-chitosan. A thin film of the novel hybrid material was produced by casting the nanocomposite solution in a petri dish. Several instrumental methods, including Fourier-transform infrared (FTIR), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD), were used to analyze and characterize the structure of the BaO-CS nanocomposite. The chemical interaction with barium oxide molecules resulted in a noticeable displacement of the most significant chitosan-specific peaks in the FTIR spectra. When the surface morphology of SEM graphs was analyzed, a dramatic morphological change in the chitosan surface was also discovered; this morphological change can be attributed to the surface adsorption of BaO molecules. Additionally, the patterns of the XRD demonstrated that the crystallinity of the material, chitosan, appears to be enhanced upon interaction with barium oxide molecules with the active sites, OH and NH2 groups, along the chitosan backbone. The prepared BaO-CS nanocomposite can be used successfully as an effective heterogenous recyclable catalyst for the reaction of N,N'-(alkane-diyl)bis(2-chloroacetamide) with 2-(arylidinehydrazine)-1-carbothioamide as a novel synthetic approach to prepare 2-hydrazonothiazol-4(5H)-ones. This new method provides a number of benefits, including quick and permissive reaction conditions, better reaction yields, and sustainable catalysts for multiple uses.

Synthesis and Molecular Docking of Some Novel 3-Thiazolyl-Coumarins as Inhibitors of VEGFR-2 Kinase.

One crucial strategy for the treatment of breast cancer involves focusing on the Vascular Endothelial Growth Factor Receptor (VEGFR-2) signaling system. Consequently, the development of new (VEGFR-2) inhibitors is of the utmost importance. In this study, novel 3-thiazolhydrazinylcoumarins were designed and synthesized via the reaction of phenylazoacetylcoumarin with various hydrazonoyl halides and α-bromoketones. By using elemental and spectral analysis data (IR, 1H-NMR, 13C-NMR, and Mass), the ascribed structures for all newly synthesized compounds were clarified, and the mechanisms underlying their formation were delineated. The molecular docking studies of the resulting 6-(phenyldiazenyl)-2H-chromen-2-one (3, 6a-e, 10a-c and 12a-c) derivatives were assessed against VEGFR-2 and demonstrated comparable activities to that of Sorafenib (approved medicine) with compounds 6d and 6b showing the highest binding scores (-9.900 and -9.819 kcal/mol, respectively). The cytotoxicity of the most active thiazole derivatives 6d, 6b, 6c, 10c and 10a were investigated for their human breast cancer (MCF-7) cell line and normal cell line LLC-Mk2 using MTT assay and Sorafenib as the reference drug. The results revealed that compounds 6d and 6b exhibited greater anticancer activities (IC50 = 10.5 ± 0.71 and 11.2 ± 0.80 µM, respectively) than the Sorafenib reference drug (IC50 = 5.10 ± 0.49 µM). Therefore, the present study demonstrated that thiazolyl coumarins are potential (VEGFR-2) inhibitors and pave the way for the synthesis of additional libraries based on the reported scaffold, which could eventually lead to the development of efficient treatment for breast cancer.

Synthesis and In Silico Study of Some New bis-[1,3,4]thiadiazolimines and bis-Thiazolimines as Potential Inhibitors for SARS-CoV-2 Main Protease.

A novel series of bis-[1,3,4]thiadiazolimines, and bis-thiazolimines, with alkyl linker, were synthesized through general routes from cyclization of 1,1'-(hexane-1,6-diyl)bis(3-phenylthiourea) and hydrazonoyl halides or α-haloketones, respectively. Docking studies were applied to test the binding affinity of the synthesized products against the Mpro of SARS-CoV-2. The best compound, 5h, has average binding energy (-7.50 ± 0.58 kcal/mol) better than that of the positive controls O6K and N3 (-7.36 ± 0.34 and -6.36 ± 0.31 kcal/mol). Additionally, the docking poses (H-bonds and hydrophobic contacts) of the tested compounds against the Mpro using the PLIP web server were analyzed.

Synthesis and Mesomorphic and Electrical Investigations of New Furan Liquid Crystal Derivatives.

New homologues set liquid crystalline materials, based on furfural derivatives, namely, (E)-4-((furan-2-ylmethylene)amino)phenyl 4-alkoxybenzoate (F n), were synthesized and investigated for their mesomorphic and optical characteristics. The prepared homologues series constitutes three derivatives that bear different terminal flexible alkyl chain lengths that vary between 6 and 12 carbons and attached to the phenyl ring linked to the ester group. A furfural moiety is introduced into the other terminal of the molecular structure. Mesomorphic characterizations of the prepared derivatives were measured using differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Molecular structures were elucidated via elemental analyses, FTIR, and NMR spectroscopy. DSC and POM showed that all the synthesized furfural derivatives are purely nematogenic, exhibiting an enantiotropic nematic (N) mesophase, except for the longest chain derivative (F 12) that is dimorphic possessing a monotropic smectic A phase and an enantiotropic N mesophase. Results indicated that the incorporation of the heterocyclic furfural ring into the molecular skeleton affected both the mesophase range and stability of investigated homologue. Analysis of the optical properties revealed that the shortest chain compound (F 6) possesses two direct band gaps, at 2.73 and 3.64 eV, in addition to higher absorption than the higher homologues, F 10 and F 12. On the other hand, all the synthesized homologues (F n) showed Ohmic behaviors, with electric resistances in the GΩ range. The values of the electrical resistances are 103.71, 12.91, and 196.85 GΩ at 0.05 V for F 6, F 10, and F 12, respectively.

New nematogenic conical-shaped supramolecular H-bonded complexes for solar energy investigations.

New conical-shaped geometrical supramolecular H-bonded liquid crystal complexes were formed through 1:2 intermolecular interactions of H-bonding between flexible core (adipic acid, A) and lateral chloro-substituted azopyridines (Bn). The chains of the terminally alkoxy substituted base (n) were changed between 8 and 16 carbons. Mesomorphic and optical examinations of the prepared complexes were measured via differential scanning calorimetry (DSC) and polarizing optical microscopy (POM). Fourier-transform infrared spectroscopy (FT-IR) was used to confirm the Fermi bands of the H- bonding interactions. Induced nematogenic mesophases that cover the whole lengths of alkoxy-chains were detected. The non-linear geometries of the designed supramolecular complexes were also confirmed via Density functional theory (DFT) calculations. It was found that the length of terminal alkoxy chain of the base moiety highly affects the geometrical structure of the investigated complexes. Moreover, it increases the thermodynamic energy and influences the geometrical parameters. The electrical properties of each of the acid component (A), the base (B16) and their 1:2 complex (A/2B16) were evaluated using the Keithley measurement-source unit. The optical properties studies showed that the influences in the optical absorption and the reduction of the energy gap of the complex compared to its individual components made the resulted supramolecular H-bonded complex soft material suitable for solar energy investigations.

Optical investigations and photoactive solar energy applications of new synthesized Schiff base liquid crystal derivatives.

New homologues series of liquid crystalline materials namely, (E)-3-methoxy-4-[(p-tolylimino)methyl]phenyl 4-alkloxybenzoates (I-n), were designed and evaluated for their mesomorphic and optical behavior. The prepared series constitutes three members that differ from each other by the terminally attached alkoxy chain group, these vary between 6 and 12 carbons. A laterally OCH3 group is incorporated into the central benzene ring in meta position with respect to the ester moiety. Mesomorphic characterizations of the prepared derivatives are conducted using differential scanning-calorimetry (DSC), polarized optical-microscopy (POM). Molecular structures were elucidated by elemental analyses and NMR spectroscopy. DSC and POM investigations revealed that all the synthesized derivatives are purely nematogenic exhibiting only nematic (N) mesophase, except for the longest chain derivative (I-12) that is dimorphic possesses smectic A and N phases. Moreover, all members of the group have a wide mesomorphic range with high thermal nematic stability. A comparative study was established between the present derivative (I-6) and their previously prepared isomer. The results indicated that the location exchange of the polar compact group (CH3) influences the N mesophase stability and range. The electrical measurements revealed that all synthesized series I-n show Ohmic behaviors with effective electric resistances in the GΩ range. Under white light illumination, the effective electric conductivity for the compound I-8 is five times that obtained in dark conditions. This derivative also showed two direct optical band gaps in the UV and visible light range. In addition, I-6 has band energy gaps of values 1.07 and 2.79 eV, which are suitable for solar energy applications.

Synthesis, Optical Characterizations and Solar Energy Applications of New Schiff Base Materials.

A new set of laterally OCH3-substituted photoactive liquid crystalline analogues, 4-hexyloxy phenyl- imino-4'-(3-methoxyphenyl)-4''-alkoxybenzoates, were synthesized and investigated for their mesomorphic behavior. The prepared set constitutes five analogues that differ from each other by the terminally attached compact polar group. Characterization of the synthesized derivatives is conducted using differential scanning calorimetry (DSC), polarized optical microscopy (POM), and UV-spectroscopy. Molecular structures were elucidated by elemental analyses, FT-IR and NMR spectroscopy. DSC and POM investigations indicated that all the prepared derivatives are monomorphic possessing the nematic (N) phase, except for the unsubstituted derivative that is nonmesomorphic. On the other side, the photophysical study and the optical spectra measurements confirm the photoactivity of the present compounds under UV/visible irradiation. The measured optical spectra showed impressive enhancement in the optical absorption and reduction in the optical bandgap from 3.63 to 3.0 eV depending on the terminal group. From the study of the DC electric properties, the lowest resistance, 106.5 GΩ at scan rate 0.1 V/s, was observed for the I6d film with Cl terminal, which decreased to 49.5 GΩ by increasing the scan rate to 0.5 V/s. Moreover, the electrical conductance is decreased from 9.39 pS to 1.35 pS at scan rate 0.1 V/s by changing the terminal group from Cl to F. The enhanced optical absorption and the reduced energy gap make the optimized samples suitable material for solar energy applications.

Cross-Linked Chitosan/Multi-Walled Carbon Nanotubes Composite as Ecofriendly Biocatalyst for Synthesis of Some Novel Benzil Bis-Thiazoles.

Aminohydrazide cross-linked chitosan (CLCS) and its MWCNTs (CLCS/MWCNTs) were formulated and utilized as a potent ecofriendly basic heterogeneous biocatalyst under ultrasonic irradiation for synthesis of two novel series of benzil bis-aryldiazenylthiazoles and benzil bis-arylhydrazonothiazolones from the reaction of benzil bis-thiosemicarbazone with 2-oxo-N'-arylpropanehydrazonoyl chlorides and ethyl 2-chloro-2-(2-phenylhydrazono) acetates, respectively. The chemical structures of the newly synthesized derivatives were elucidated by spectral data and alternative methods, where available. Additionally, their yield % was estimated using a traditional catalyst as TEA and green recyclable catalysts as CLCS and CLCS/MWCNTs composite in a comparative study. We observed that, under the same reaction conditions, the yield % of the desired products increased by changing TEA to CLCS then to CLCS/MWCNT from 72-78% to 79-83% to 84-87%, respectively. The thermal stability of the investigated samples could be arranged as CLCS/MWCNTs composite > CLCS > chitosan, where the weight losses of chitosan, CLCS and CLCS/MWCNTs composite at 500 °C were 65.46%, 57.95% and 53.29%, respectively.