Ultrasonic-induced synthesis of novel diverse arylidenes via Knoevenagel condensation reaction. Antitumor, QSAR, docking and DFT assessment.

A series of arylidenes derivatives was synthesized under ultrasonic methodology via Knoevenagel condensation reaction of cyanoacetohydrazide derivative with the appropriate aldehydes and/or ketone. The anticancer properties of the newly synthesized compounds were tested against four different human cancer cell lines (HEPG-2, MCF-7, HCT-116, and PC-3); compounds 5d and 6 demonstrated the greatest anticancer activity against all cancer cell lines. The MLR technique was used to create the QSAR model using five molecular descriptors (AATS6p, AATS7p, AATS8p, AATS0i, and SpMax4_Bhv). The examination of the constructed QSAR model equations revealed that the selected descriptors influence the tested compound's anti-proliferative activity. The descriptors identified in this work by QSAR models can be utilized to predict the anticancer activity levels of novel arylidenes derivatives. This will allow for significant cost savings in the drug development process and synthesis at pharmaceutical chemistry laboratories. According to the physicochemical properties, the results revealed that all of these compounds comply with Lipinski's Rule of Five, indicating that they may have high permeability across biological membranes and reveal drug-relevant properties. The Swiss Target Prediction webtool was used to assess the probable cellular mechanism for the promising candidate compounds (5d and 6), and the results revealed that adenosine A1 receptor (ADORA1) was a common target for both compounds. ADORA1 is involved in the regulation of cell metabolism and gene transcription. ADORA1 overexpression has been linked to a variety of cancers, including colon cancer, breast cancer, leukemia, and melanoma. The docking study of tested compounds 5d and 6 revealed that their binding scores to ADORA1 are more favorable than those of its co-crystalized ligand (DU172, selective ADORA1 antagonist) and adenosine (ADORA1 endogenous agonist), implying that they may hold great promise as an anti-cancer therapy. Density functional theory (DFT) with a (B3LYP)/6-31G (d,p) basis set was used to calculate the physicochemical parameters of these compounds. The theoretical data from the DFT computation was found to be in good agreement with the experimental values.

Synthesis, antimicrobial activities, docking studies and computational calculations of new bis-1,4-phenylene -1H-1,2,3-triazole derivatives utilized ultrasonic energy.

In this elucidation, we studied the utility of condensation reaction between 1,4-phenylenediamine (1) with acetyl acetone (2) with hydrazine hydrate utilized ultrasonic energy in one step reaction to afford the corresponding 1,1'-(1,4-phenylenebis (5-methyl-1H-1,2,3-triazole-1,4-diyl))bis(ethan-1-one) (4) in excellent yield. The ethanol solution of bis triazole (4) and different aldehyde derivatives were sonicated at 75 °C for 2 h to afford chalcone derivatives 5a-d which were confirmed via spectral data such as FTIR, 1HNMR, 13CNMR and mass spectra. Moreover, the intermolecular cyclization of chalcone (5a) with NH2NH2 in sodium hydroxide solution to give the corresponding 4,5-dihydro-1H-pyrazol-5-yl)-1H-indole (6) using ultrasonic energy for 4 h, while the Michael addition of chalcones (5a) and (5 b) with thiourea in basic condition to afford the corresponding pyrimidine-2-thiol derivatives (7) and (9). Treatment of compound (7) with NH2NH2 to afford 1,4-bis(4-(2-hydrazineyl-6-(1H-indol-3-yl)pyrimidin-4-yl) derivatives (8). The synthesized compounds were screened against various microbial strains and displayed excellent antimicrobial potential. Additionally, the docking studies of these nine compounds were carried out with (PDB ID:3t88), (PDB ID:2wje), (PDB ID:4ynt) and (PDB ID:1tgh) which were attached with different amino acids with shortage bond length, and it was noticed that PMTS1, PMTS2 and PMTS3 were the most stable compounds with the lowest energy affinity which is compatible with biological study. Furthermore, the theoretical investigation of bis-triazole compounds were optimized via DFT/B3LYP/6-31G(d) level which showed the hyperconjugation of nitrogen atoms and elucidated their physical parameters and NBO charges and confirmed their stability and biological activity.Communicated by Ramaswamy H. Sarma.

Synthesis, Phase Behavior and Computational Simulations of a Pyridyl-Based Liquid Crystal System.

A homologous set of liquid crystalline materials (Tn) bearing Schiff base/ester linkages were prepared and investigated via experimental and theoretical techniques. Terminal flexible groups of different chain lengths were connected to the end of phenylbenzoate unit while the other end of molecules was attached to the heterocyclic pyridine moiety. The molecular structures of the designed molecules were evaluated by FT-IR, NMR spectroscopic analyses, whereas their mesomorphic properties were investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). They all exhibited dimorphic properties with the exception of the members having the shortest and longest terminal flexible chains (n = 6 and 16), which were monomorphic. The T16 derivative was further found possessing purely smectic A (SmA) mesophase while others have their lengths covered by nematic (N) phase. Moreover, the computational evaluation of the azomethine derivatives was carried out using a DFT approach. The polarity of the investigated derivatives was predicted to be appreciably sensitive to the size of the system. Furthermore, the Frontier molecular orbitals analysis revealed various distributions of electron clouds at HOMO and LUMO levels.

Polyaconitic acid/functional amine/azo dye composite as a novel hyper-branched polymer for cotton fabric functionalization.

A new hyperbranched polymer based on aconitic acid and two different amine (triethnaol amine and diethylenetriamine) with different functional groups; hydroxyl and amine groups respectively was successfully synthesised by A2B3 polymerization technique and characterised using Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR), rheological properties, antimicrobial and cytotoxicity activity. In addition, a new heterocyclic azo dye was synthesised and characterised using FT-IR, NMR, mass spectra and antimicrobial activity. Characterisation provides that both composites and azo dye have been well prepared. A mixture from both hyberbranched polymer and synthesised azo dye have been applied to cotton fabrics. Evaluation of treated fabrics shows that, the surface of treated fabrics has a thin film from applied composite which coated the whole fibre surface. Treated fabrics have good antimicrobial activity against gram positive, gram negative bacteria and fungi. Fastness properties, physical and mechanical properties for treated fabrics were also evaluated.

Ball Milling Promoted N-Heterocycles Synthesis.

In the last years, numerous protocols have been published using ball milling for organic synthesis. Compared to other methods such as microwave or ultrasound irradiation and ionic liquids, ball mill chemistry is an economical, and ecofriendly method in organic synthesis that is rather underrepresented in the knowledge of organic chemists. The aim of this review is to explore the advantages of the application of ball milling in synthesis of N-heterocyclic compounds.

Ball Milling Assisted Solvent and Catalyst Free Synthesis of Benzimidazoles and Their Derivatives.

Benzoic acid and o-phenylenediamine efficiently reacted under the green solvent-free Ball Milling method. Several reaction parameters were investigated such as rotation frequency; milling balls weight and milling time. The optimum reaction condition was milling with 56.6 g weight of balls at 20 Hz frequency for one hour milling time. The study was extended for synthesis of a series of benzimidazol-2-one or benzimidazol-2-thione using different aldehydes; carboxylic acids; urea; thiourea or ammonium thiocyanate with o-phenylenediamine. Moreover; the alkylation of benzimidazolone or benzimidazolthione using ethyl chloroacetate was also studied.

Ultrasonic Synthesis, Molecular Structure and Mechanistic Study of 1,3-Dipolar Cycloaddition Reaction of 1-Alkynylpyridinium-3-olate and Acetylene Derivatives.

Regioselectively, ethyl propiolate reacted with 1-(propergyl)-pyridinium-3-olate to give two regioisomers; ethyl 4-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-2,6-diene-6-carboxylate 4, ethyl 2-oxo-8-(prop-2-ynyl)-8-aza-bicyclo(3.2.1)octa-3,6-diene-6-carboxylate 5 as well as ethyl 2,6-dihydro-6-(prop-2-ynyl)furo(2,3-c)pyridine-3-carboxylate 6. The obtained compounds were identified by their spectral (IR, mass and NMR) data. Moreover, DFT quantum chemical calculations were used to study the mechanism of the cycloaddition reaction. The regioselectivity was explained using transition state calculations, where the calculations agreed with the formation of products 4 and 5 in almost the same ratio. The reaction was also extended for diphenylaceylene as dipolarophile to give only two products instead of three.