Letters in Organic Chemistry - Volume 18, Issue 10, 2021

Tetrac, a deaminated derivative of the thyroid hormome, has received some broad interest for its ability to inhibit the spread of new blood vessels, i.e., angiogenesis. For an optimum activity, the action of the dug shall be limited at the cell surface for interaction with the integrin alpha v beta 3. This was shown to be achieved via a nanoparticle formulation that would be grafted to Tetrac phenol’s OH. While the principle of this study has been disclosed elsewhere, the broad results have never been disclosed entirely. Here all outcomes of the synthesis strategy, e.g., protection and activation steps, confirmed Triisopropylsillyl as a protective group of choice to access the nanoparticle. Catalyst assisted esterification has been probed and discussed. Then the HPLC-MS study allowed to clarify reaction conditions that could subsequently yield to the desired activated Tetrac moiety. The reaction products were all characterized by 1H and 13C-NMR.

A series of 2-heteroaryl benzimidazole-chalcone hybrids were synthesized and the anticancer activity was estimated by MTT assay in human breast, lung, colon, and ovarian cancer cell lines. The biological results indicate that the compounds showed good anticancer activity with IC50 value in the range of 0.056-19.5 μM. Compound 11b with hexa methoxy groups, bearing three methoxy groups on each terminal aryl ring exhibited a significant IC50 value (56 nM) against human breast carcinoma cells, which is 37 times higher potency in comparison with the reference Etoposide. Further compounds substituted variably with methoxy and nitro groups on the phenyl ring of chalcone showed more promising anticancer activity than the compounds with unsubstituted phenyl ring or variably alkyl-substituted phenyl ring of chalcone. The molecular docking results indicate that the synthesized compounds bind in the active site of Abl tyrosine kinase, the target of anticancer drug Imatinib. The present study provides the synergistic effect of hybrids, benzimidazole-chalcones as potential anticancer agents that will aid in the discovery of new anticancer agents.

An efficient Ag-promoted decarboxylative cyclization of α-oxocarboxylic acids with (E)-3- (2-aminophenyl)-1-phenylprop-2-en-1-ones has been developed to afford a series of functionalized quinolines in moderate to good yields. This method was compatible with a variety of functional groups and provided an attractive method toward phenyl(2-phenylquinolin-3-yl)methanones.

In recent years, substitution at the third position on phthalides has been proven a valuable synthetic intermediate for developing active molecules. We reported a direct and efficient onepot method for the synthesis of 3-aryl Phthalides performed by adding organo-zinc reagent on methyl-2-formylbenzoate; reagent formed in-situ by the reaction between diethylzinc and different aryl boronic acid derivatives without using any ligand. The possible mechanism involved a coordinated zinc carbonyl transition state, arylation, and followed by the intramolecular cyclization. The substituents groups in boronic having different electronic and steric properties played an important role in the reaction completion time and yield. The structure elucidation and confirmation of the synthesized compounds were done by using H-NMR analytical data. The method can be useful for synthesizing various scaffolds and intermediates in search of potentially active compounds.

An efficient synthesis of 2-substituted Quinazolin-4(3H)-ones has been developed from isatoic anhydride with various amidoximes by using a recyclable polymer-supported sulphonic acid catalyst. Excellent functional group compatibility and high yields are the important features of this protocol.

N-(2-Bromoethyl) succinimide (N2BES) is a compound with antidepressant pharmacological properties. N-(2-Bromoethyl) succinimide was analyzed for its structural, electronical, vibrational, topological, and biological properties. The molecular geometrical parameters such as bond lengths (Å), bond angles (º), and dihedral angles (º) of N2BES and harmonic vibrational frequencies were investigated using the density functional theory calculations with the B3LYP/6-311++G(d,p) level of theory. Experimental vibrational frequencies of N2BES were recorded in the region of 4000–400 cm-1 (FT-IR) and 4000–100 cm-1 (FT-Raman) and compared with the theoretical frequencies on the basis of potential energy distribution (PED) analysis. Frontier molecular orbitals (FMOs), global reactivity descriptors, the density of states (DOS) properties, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, topological analysis of the reduced density gradient (RDG), localized orbital locator (LOL), and bond critical points (BCP) for N2BES were investigated by theoretical calculations. The experimental UV-Vis was measured within 200-500 nm and electronic transitions of absorption wavelength (λ), excitation energies (E), oscillator strengths (f), and ethanol solvent were calculated. In addition, the molecular docking study of the title molecule predicted its binding orientation in the active site of the target serotonin 1A (5-HT1A) protein.

The process of hydrogen bond donor accelerating the cycloaddition of epoxides with CO2 is a green conversion. In this text, commercial drug flufenamic acid which contains O-H and N-H groups is introduced to promote the coupling. The reaction is capable of tolerating a relatively wide range of groups with the aid of catalytic system flufenamic acid/TBAB. Moreover, the reaction mechanism is proposed on the basis of reported literatures.

Since the ethylacetate (EtOAc) extract of the roots of Zhumeria majdae had the potent cytotoxic effect (IC50 < 50 μg/ml) on three cancer cell lines; MCF-7, PC3 and MDAMB- 231, therefore the purpose of this study was the isolation of the responsible cytotoxic compounds from the plant. Isolation of the extract led to the identification of four diterpenoids named as lanugon Q (1), 12,16-dideoxy aegyptinone B (2), 12-deoxysalvipisone (3) and manool (4). The chemical structures have been determined on the basis of 1D and 2D NMR experiments. Compound 1 is reported for the first time in the plants of the Zhumeria genus. The results of cytotoxic and apoptotic evaluation revealed that compound 2 had a strong cytotoxic effect with the IC50 value of 15.90 μg/ml against MCF-7 cell lines. The sub-G1 peak in flow cytometry histogram of cells treated with the EtOAc extract and compound 2 showed the induction of apoptosis. Changes in the Bax/Bcl-2 ratio and cleavage of PARP were observed. It is to be noted that owing to the strong cytotoxic effect, the Z. majdae extract could be represented as a therapeutic agent against cancer.

In the present study, a series of 2,5-disubstituted-1,3,4 oxadiazole analogues retaining pyridine moiety were synthesized (4a-j) by reacting various substituted aromatic acids and isonicotinohydrazide by using POCl3 as a cycling agent. The structure elucidation of all the synthesized compounds was done by chromatographic data and spectral data analysis. The synthesized compounds were evaluated for their in-vitro antimicrobial activity against various strains of ESKAPE pathogens. Antibacterial activity was performed against Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, while antifungal activity was assayed against Candida albicans and Aspergillus spp. The result of in-vitro antimicrobial studies of all the synthesized compounds revealed that compound 4d and 4f exhibited promising activity against selected microbial strains equally compared to Cefixime and Econazole used as reference drugs.

In this study, 3-alkyl(aryl)-4-(4-ethylbenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones 2 were synthesized as explained in the literature. Then, the Schiff bases 2 were treated with morpholine/ N-methylpiperazine/ 3-methylpiperidine/ 4-piperidinecarboxamide in the presence of formaldehyde according to the Mannich reaction to synthesize novel Mannich bases 3, 4, 5, and 6 types, respectively. The structural analyses of 24 newly synthesized compounds were characterized using proton/ carbon 13 nuclear magnetic resonance (1H/ 13C-NMR), Infrared (IR) spectoscopic techniques. In addition, the antimicrobial activity of the compounds was determined on six bacteria by using the agar well diffusion method. The most effective results against gram positive and negative bacteria were observed in 6(a-d) and 6f compounds. Also, the antioxidant capacities of the substances were investigated by three different methods (DPPH, reducing power, metal chelation). All compounds 3-6(a-f) showed a metal chelating effect.