Synthesis, conformational analysis and antimicrobial activity of 10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indole acyclo C-nucleoside analogs.

Condensation of 5-benzyl-3-hydrazino-1,2,4-triazino[5,6-b]indole with various sugar aldoses or ketoses gave the corresponding sugar hydrazones as single geometrical isomer or exist in E/Z tautomeric isomers. The hydrazones underwent heterocyclization with Fe(Ш)Cl3 to give the N2-adduct acyclo C-nucleosides: 3-(alditol-1yl)-10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indoles rather than the N4-adduct: 10-(alditol-1-yl)-3-benzyl-1,2,4-triazolo[3,4-c]1,2,4-triazino[5,6-b] indoles on the basis of chemical and UV spectral proofs. Conformational analysis of their polyacetates were studied. The new acyclo C-nucleosides were evaluated for antimicrobial activity.

Spectroscopic details on the molecular structure of pyrimidine­2­thiones heterocyclic compounds: computational and antiviral activity against the main protease enzyme of SARS-CoV-2.

Computational tools in investigating of spectral heterocyclic compounds ranges based on pyrimidine­2­thiones, take some importance in identifying their molecular and electronic behavior. Some charcoal heterocyclic compounds were previously synthesized in our laboratory and their experimental results were compared with the computational evaluation. Computational spectroscopic analytical items (IR, NMR and UV-Vis) were calculated using the more popular DFT methods and the predicted results were compared with the reported experimental ones. Quantum and chemical parameters were calculated and molecular electrostatic surface potential (MEP) was studied which predicted the highly electronic sites around the compounds. Some molecular properties (ionization energy, electron affinity, energy gap, hardness, electronegativity, electrophilicity index, static dipole moment and average linear polarizability) of these Schiff bases which were computed at B3LYP/6-31G(d,p) level in aqueous phase. Benchmark analysis was performed for three ab initio functionals such B3LYP, BPV86 and B3PW91 methods to explain the data resulted from NMR spectra. The docking study of some selected previously synthesized compounds was performed using the viral Mpro enzyme protein in compared to a k36 reference ligand inhibitor. The study indicated the ability of the synthesized compounds to form H-bond and hydrophobic (VDW, π-alkyl and π-sulfur) interactions with Mpro enzyme receptor with high inhibition effect of compound L2.

Synthesis and Antimicrobial Activity of 1,3,4-Oxadiazoline, 1,3-Thiazolidine, and 1,2,4-Triazoline Double-Tailed Acyclo C-Nucleosides.

The condensation products of terphthaloyl bishydrazide with two equivalents of various monosaccharide aldoses were found to have a bis(sugarhydrazone) form or bis-glycosylhydrazide structure or coexist in tautomeric equilibrium depending on the sugar configuration. The condensation products were substantially utilized as 3-acetyl-1,3,4-oxadiazoline, 1,3-thiazolidine, and 4-amino-1,2,4-triazoline double-tailed acyclo C-nucleosides synthons. The preliminary antimicrobial activities of representative examples of the prepared compounds were evaluated.

Synthesis, screening as potential antitumor of new poly heterocyclic compounds based on pyrimidine-2-thiones.

BACKGROUND: Continuing our interest in preparing of new heterocyclic compounds and examining their various biological activities, this work was designed to prepare new condensed and non-condensed heterocyclic compounds 9a-c, 10a-c, 11a-c, 13a-c and 14a-c were synthesized starting with pyrimidine-2-thiones 4a-c. RESULTS: Thiazolo[3,2-a]pyrimidines 9a-c were synthesized by S-alkylation of pyrimidine-2-thiones,4a-c, internal cyclization in alkaline medium with ammonia, condensation with benzaldehyde and finally reaction with hydroxylamine hydrochloride.[1,2,4]thiadiazolo[4,5-a]pyrimidines 11a-c were formed by heating of the 4a-c with benzoylcholride to afford 10a-c followed by reaction with sodium hypochlorite, ammonia and sodium hydroxide. Cyclocondensation of 4a-c with ethyl acetoacetate or formic acid yielded pyrazol-3-ones 13a-c or [1,2,4] triazolo[4,3-a]pyrimidines 14a-c, respectively Elements analysis, IR, 1H-NMR, 13C-NMR and mass spectra were used to validate the structures of newly synthesized heterocycles. Screening of the selected compounds 4a, 6a, 7a, 9a, 10a, 13a and 14a against colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2). CONCLUSIONS: Elements analysis, IR, 1H-NMR, 13C-NMR and mass spectra were used to validate the structures of newly synthesized heterocycles. Screening of the selected compounds 4a, 6a, 7a, 9a, 10a, 13a and 14a against colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2) showed that compound 10a exhibited the most cytotoxic, while compounds 4a, 6a and 14a exhibited considerable cytotoxic activity.

Computational details of molecular structure, spectroscopic properties, topological studies and SARS-Cov-2 enzyme molecular docking simulation of substituted triazolo pyrimidine thione heterocycles.

Investigation the molecular structure of the system requires a detailed experience in dealing with theoretical computational guides to highlight its important role. Molecular structure of three heterocyclic compounds 8,10-diphenylpyrido[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (HL), 8-phenyl-10-(p-tolyl)pyrido[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (CH3L) and10-(4-nitrophenyl)-8-phenylpyrido[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine-3(2H)-thione (NO2L) was studied at DFT/B3LYP/6-31G (d,p) level in ethanol solvent. Spectroscopic properties such Infrared (IR, 1H NMR and 13C NMR) and ultraviolet-visible (UV-VIS) analyses were computed. Some quantum and reactivity parameters (HOMO energy, LUMO energy, energy gap, ionization potential, electron affinity, chemical potential, global softness, lipophelicity) were studied, also molecular electrostatic potential (MEP) was performed to indicate the reactive nucleophilic and electrophilic sites. The effects of H-, CH3- and NO2- substituents on heterocyclic ligands were studied and it was found that the electron donation sites concerned with hydrogen and methyl substituents over nitro substituent. Topological analysis using reduced density gradient (RDG) was discussed in details. To predict the relevant antiviral activity of the reported heterocyclic compounds, molecular docking simulation was applied to the crystal structure of SARS-Cov-2 viral Mpro enzyme with 6WTT code and PLpro with 7JRN code. The enzymatic viral protein gives an image about the binding affinity between the target protein receptor and the heterocyclic ligands entitled. The hydrogen bonding interactions were evaluated from molecular docking with different strength for each ligand compound to discuss the efficiency of heterocyclic ligands toward viral inhibition.

Synthesis and Screening of New [1,3,4]Oxadiazole, [1,2,4]Triazole, and [1,2,4]Triazolo[4,3-b][1,2,4]triazole Derivatives as Potential Antitumor Agents on the Colon Carcinoma Cell Line (HCT-116).

New derivatives of [1,3,4]oxadiazole-2-thione and triazole-3-thione were synthesized through the cyclocondensation of dicarbonyl ester 2 with phenyl hydrazine followed by hydrazinolysis to give the corresponding hydrazide, which reacted with carbon disulfide or ammonium thiocyanate to afford [1,3,4]oxadiazole 5 or triazole-3-thione 7, respectively. Hydrazinolysis of compound 5 gave [1,2,4]triazole-3-thiol 9 which was treated with different aromatic aldehydes to obtain 10a-c. Mannich bases 11a-c were obtained from the reaction of Schiff bases 10a-c with morpholine and formaldehyde. Moreover, treatment of triazole-3-thione 7 with hydrazine was followed by cyclocondensation with diethyl oxalate, chloroacetic acid, or formic acid to give the corresponding [1,2,4]triazine-3,4-dione 14, [1,2,4]triazin-4-one 15, or [1,2,4]triazolo[4,3-b][1,2,4] triazole 16, respectively. Screening of some chosen synthesized compounds against the human colon carcinoma cancer cell lines showed that the compound [1,2,4]triazole-3-thiol 9 exhibiting cytotoxic activity was roughly equivalent to standard Vinblastine, while compounds 4, 7, 10, 11a, 14, and 16 exhibited moderate cytotoxic activity.

Synthesis of Some New Heterocyclic Azo Dyes Derived from 2-amino-3-cyano-4.6- diarylpyridines and Investigation of its Absorption Spectra and Stability using the DFT.

INTRODUCTION: In continuation of our interest in 2-amino-3-cyano-4.6-diarylpyridines reactions in various fields of organic chemistry which were previously used for the synthesis of many heterocyclic compounds and where dyes generally have many applications especially when benzene or anthraquinone azo dyes are replaced with heterocyclic azo dyes so new derivatives of heterocyclic azo dyes derived from 2-amino-3-cyano- 4.6-diarylpyridines were prepared. MATERIALS AND METHODS: The IR spectra (KBr), NMR, elemental microanalyses and mass spectra, were performed at different faculties of science in Egypt. Absorption spectra were recorded on Unicam SP 750 in DMF and acetone using 1x 10-5 mol l-1 of dye concentration. Optimization was performed using density functional theory (DFT) and time dependent-DFT by applying Becke's three-parameter hybrid exchange functional with Lee- Yang-Parr gradient-corrected correlation (B3LYP functional). The chemical reagents used in the synthesis were purchased from Fluka, Sigma and Aldrich. RESULTS AND DISCUSSION: The structure of the preparing Heterocyclic azo dyes is proven using spectroscopic tools and elemental analysis, and investigation of its absorption spectra indicate the effect of both solvent and substituent on absorption maximum. DFT calculations were performed on some of the selected dyes. CONCLUSION: Structures of newly synthesized heterocyclic azo dyes were confirmed using elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectral data. DFT theory was used in explaining the electronic properties of some selected dyes, where the energy gap can help in understanding the reactivity behaviour and stability of these compounds. Absorption spectra indicate the effect of both solvent and substituent on absorption maximum.

A New Synthesis of Poly Heterocyclic Compounds Containing [1,2,4]triazolo and [1,2,3,4]tetrazolo Moieties and their DFT Study as Expected Anti-cancer Reagents.

BACKGROUND: 2-amino-3-cyanopyridines are good starting reagents that have been used in synthesis of many heterocyclic compounds such as pyridopyrimidines, [1,2,4]triazolo and [1,2,3,4] tetrazolo derivatives which have biological activities as anti-microbial and cytotoxic activities. Meanwhile [1,2,4]triazolo and [1,2,3,4]tetrazolo derivatives are well known to possess many physiological activities, such as anticancer , antifungal, muscle relaxant, hypnotic, anti-inflammatory, diuretic and antihypertensive activities. A broad class of heterocyclic compounds has been studied to demonstrate their biological activity on the structures of DNA and RNA. Several of important functions make Tankyrases acts as targets in potential drug. OBJECTIVE: The article focuses on synthesis of [1,2,4]triazolo and [1,2,3,4]tetrazolo derivatives and their theoretical calculations that suggest they are anti-cancer substances. MATERIALS AND METHODS: DFT and computational studies were performed on the structural properties of experimental molecules experimentally, and significant theoretical calculations were performed based on density functional theory (DFT) with Becke's three-parameter exchange function21-22 of correlation functional Lee Yang Parr (B3LYP) with the basis set 6-31G (d,p) using Gaussian 03 software23. Geometrical parameters of the optimized structures were calculated and also the charge on each atom (Mulliken charge). Chemcraft program24 was used to visualize the optimized structure and ChemBio3D ultra 12.0 was used to visualize the highest occupied and lowest unoccupied molecular orbitals. RESULTS: Preliminary screening in five studied ligands acts as inhibitors for different active sites along the target. The molecular docking study also revealed that the compound 6c was the most effective compounds in inhibiting Tankyrase I enzyme (2rf5), this result can help strongly in inhibition of carcinogenic cells and cancer treatment. CONCLUSION: We have described a new practical cyclocondensation synthesis for a series of [1,2,4]triazolo[4,3- c]pyrido[3,2-e] pyrimidine and pyrido[2',3':4,5] pyrimido[6,1-c][1,2,4] triazine from 2-amino-3-cyano-4.6- diarylpyridines. Also polyheterocyclic compounds containing [1,2,4]triazolo and [1,2,3,4]tetrazolo moieties were also synthesized through the reactions of 3-hydrazino-8,10-diaryl [1,2,4]triazolo[4,3-c]pyrido[3,2- e]pyrimidine with both formic acid and the formation of diazonuim salt respectively. Newly synthesized heterocycles structures were confirmed using elemental analysis, IR, 1H-NMR, 13C-NMR and mass spectral data. DFT and computational studies were carried out on five of the synthesized poly heterocyclic compounds to show their structural and geometrical parameters involved in the study. Molecular docking using Tankyrase I enzyme as a target showed how the studied heterocyclic compounds act as a ligand interacting most of active sites on Tankyrase I with a type of interactions specified for H-bonding and VDW. We investigated that the five studied ligands act as inhibitors for different active sites along the target. The molecular docking study also revealed that the compound 6c was the most effective compounds in inhibiting Tankyrase I enzyme (2rf5), this result can help strongly in inhibition of carcinogenic cells and cancer treatment.

A critical study of interactive fluoride adsorption by raw marine organisms and a synthetic organic 2-amino-3-cyano-4(4-nitrophenyl)-6-phenylpyridine as adsorbent tools.

Defluoridation process using raw marine organisms and synthetic organic adsorbents was accurately studied. The marine adsorbents (algae, bivalves, sea star, brittle star, and coral reef) were collected from the Egyptian Mediterranean Sea and Red Sea. The organic adsorbent of 2-amino-3-cyano-4(4-nitrophenyl)-6-phenylpyridine was synthesized. The influence of pH, shaking time, effect of temperature and adsorbent's weight was studied. A complete fluoride removal by marine adsorbents was gained within 15-20 min. Fluoride removal procedure was evaluated by some adsorption isotherm models of linear two-parameter ((Freundlich, Tempkin, Langmuir, Flory-Huggins, Dubinin-Radushkevich, Non-ideal competitive adsorption (NICA), Brunauer-Emmett-Teller (BET), and Generalized)), nonlinear two-parameter (Langmuir and Freundlich), and nonlinear three-parameter (Redlich-Peterson, Khan, Generalized, and Toth). The most appropriate models were evaluated by error functions and statistical tests like coefficient (R2) and chi-square (χ2). Additionally, the kinetic and thermodynamic variables were calculated at variable temperatures. The results indicated that the pseudo-second-order model fitted better than the pseudo-first-order one. The negative ΔG° values confirmed that the adsorption process was favorable and spontaneous. Interestingly, this study indicated the great removal capacity of the raw organisms.