Green Biocatalyst for Ultrasound-Assisted Thiazole Derivatives: Synthesis, Antibacterial Evaluation, and Docking Analysis.

The catalytic activity of chitosan (Cs) and grafted Cs led to the preparation of terephthalohydrazide Cs Schiff's base hydrogel (TCsSB), which was then investigated as an eco-friendly biocatalyst for synthesizing novel thiazole derivatives. TCsSB exhibited greater surface area and higher thermal stability compared to Cs, making it a promising eco-friendly biocatalyst. We synthesized two novel series of thiazoles via the reaction of 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothioamide with various hydrazonoyl chlorides and 2-bromo-1-arylethan-1-ones, employing ultrasonic irradiation and using TCsSB as a catalyst. A comparative study between Cs and TCsSB revealed higher yields than TCsSB. The methodology offered advantages such as mild reaction conditions, quick reaction times, and high yields. TCsSB could be reused multiple times without a significant loss of potency. The chemical structures of the newly synthesized compounds were verified through IR, 1H NMR, 13C NMR, and MS analyses. Six synthesized compounds were assessed for their in vitro antibacterial effectiveness by establishing the minimum inhibitory concentration against four distinct bacterial strains. The docking analyses revealed favorable binding scores against several amino acids within the selected protein (PDB Code-1MBT) for these compounds, with compound 4c exhibiting particularly noteworthy binding properties. Additionally, the in silico ADME parameter estimation for all compounds indicated favorable pharmacological properties for these compounds.

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors.

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N'-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = -8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19.

Design, Synthesis, and Spectroscopic Studies of Some New α-Aminophosphonate Analogues Derived from 4-Hydroxybenzaldehyde with Special Reference to Anticancer Activity.

Introduction: As biological activity components, α-aminophosphonates and their moieties play important roles in medicinal chemistry. Alpha-phosphonic acids are significant α-amino acid counterparts. Due to its strong biological activity, this class of molecule has recently been discovered to have numerous medical applications. Results and Discussion: A new class of α-aminophosphonates and arylidene derivatives was synthesized. Various spectroscopic and elemental analyses were used to confirm the prepared products. The produced materials were tested as anticancer against breast carcinoma cells and normal human cells (PBMC). Besides the analysis results, it was found that (7b, 4c, 5k, 6, 5a, 7c, 5f, 5b, and 5g) against MCF-7 line cells. As a reference anticancer drug, 5-fluorouracil was used. The anticancer activities showed that the compounds 7b, 4c, containing α-aminophosphonate and Schiff base groups, respectively, showed high inhibition activity against the MCF-7 cell line, with 94.32% and 92.45% inhibition compared to the inhibition by 5-FU with 96.02% inhibition. The results showed that the compounds 5k, 7b, 6, and 5a, respectively, had very low activity against normal human cells PBMC, with 12.77%, 13%, 13.13%, and 17.88% inhibition compared to the inhibition by 5-FU with 12.50% inhibition. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor, thymidylate synthase, was determined using molecular docking (pdb code: 1AN5). Conclusion: α-aminophosphonate derivatives, arylidines, and disphosphonate derivatives derived from 4-hydroxybenzaldehyde were synthesized, purified, elucidated by spectroscopic analysis, and finally tested against carcinoma breast cancer to give high to moderate to low activity.

Investigation of the Anticancer Effect of α-Aminophosphonates and Arylidine Derivatives of 3-Acetyl-1-aminoquinolin-2(1H)-one on the DMBA Model of Breast Cancer in Albino Rats with In Silico Prediction of Their Thymidylate Synthase Inhibitory Effect.

Breast cancer is a major cause of death in women worldwide. In this study, 60 female rats were classified into 6 groups; negative control, α-aminophosphonates, arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, DMBA, DMBA & α-aminophosphonates, and DMBA & arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. New α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one were synthesized and elucidated by different spectroscopic and elemental analysis. Histopathological examination showed marked proliferation of cancer cells in the DMBA group. Treatment with α-aminophosphonates mainly decreased tumor mass. Bcl2 expression increased in DMBA-administered rats and then declined in the treated groups, mostly with α-aminophosphonates. The level of CA15-3 markedly declined in DMBA groups treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. Gene expression of GST-P, PCNA, PDK, and PIK3CA decreased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one, whereas PIK3R1 and BAX increased in the DMBA group treated with α-aminophosphonates and arylidine derivatives of 3-acetyl-1-aminoquinolin-2(1H)-one. The molecular docking postulated that the investigated compounds can inhibt the Thymidylate synthase TM due to high hydrophobicity charachter.

Synthesis, Characterization, Antimicrobial Activity and Anticancer of Some New Pyrazolo[1,5-a]pyrimidines and Pyrazolo[5,1-c]1,2,4-triazines.

BACKGROUND: Pyrazole and its derivatives are known to exhibit significant biological and pharmacological activities such as anticancer, anti-inflammatory, antioxidant, antibacterial, analgesic, antiviral, antimicrobial, antifungal, anti-glycemic, antiamoebic, and antidepressive. Considering the immense biological properties, pyrazole is one of the most widely studied nitrogen- containing heterocyclic nuclei. Fused pyrazole derivatives are composed of the pyrazole nucleus attached to other heterocyclic moieties. OBJECTIVE: The objective of this article is the synthesis of some new pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]1,2,4-triazine derivatives with potential anticancer and antimicrobial activities. METHODS: The in vitro growth inhibitory rates (%) and inhibitory growth activity (as measured by IC50) of the newly synthesized compounds were determined against the MCF-7 human breast carcinoma cell line in comparison with the well-known anticancer drug doxorubicin as the standard, using the MTT viability assay. The data generated were used to plot a dose-response curve from which the concentration (µM) of tested compounds required to kill 50% of the cell population (IC50) was determined. Cytotoxic activity was expressed as the mean IC50 of three independent experiments. The difference between inhibitory activities of all compounds with different concentrations was statistically significant p < 0.001. All compounds were structurally characterized by different spectroscopic techniques EI-MS, 1H-NMR, and 13C-NMR, and evaluated for their anticancer and antimicrobial activities (antibacterial and antifungal). RESULTS: Several pyrazolo[1,5-a]pyrimidine derivatives were synthesized from the reaction of 2-(4- (5-amino-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with the appropriate active methylene compounds in boiling ethanol. Also, pyrazolo[5,1-c]triazines were obtained through the reaction of 2-(4-(5-(chlorodiazenyl)-1H-pyrazol-3-yl)phenyl)-1H-indene-1,3(2H)-dione with various active methylene compounds in ethanol containing sodium acetate at 0-5 oC. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. The newly synthesized compounds were evaluated for their antitumor activity against a breast cancer cell line (MCF-7) and a human colon cancer cell line (HCT-116). The results revealed that the tested compounds showed high variation in the inhibitory growth rates and activities against the tested tumor cell lines. All newly synthesized compounds screen towards microorganisms e.g. Gram-negative bacteria, Gram-positive bacteria, and Fungi. CONCLUSION: 2-(4-(5-Amino-1H-pyrazol-3-yl)phenyl)isoindoline-1,3-dione proved to be a useful precursor for the synthesis of various pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c]-1,2,4- triazines. The structures of the newly synthesized compounds were confirmed by spectral data and elemental analyses. The newly synthesized compounds were tested in vitro against the MCF-7, HCT-116 human cancer cell line and compared with doxorubicin as the standard, using the MTT viability assay. Most of the tested compounds were found to have moderate to high anticancer activity.

Synthesis of novel thiazole, pyranothiazole, thiazolo[4,5-b]pyridines and thiazolo[5',4':5,6]pyrano[2,3-d]pyrimidine derivatives and incorporating isoindoline-1,3-dione group.

BACKGROUND: Thiazole is a core structural motif presents in a wide range of natural products. Thiazole derivatives also have a wide range of medicinal and biological properties. RESULTS: The reaction of hydrazonoyl halides with 2-(1-(4-(1,3-dioxoisoindolin-2-yl)phenyl)ethylidene)hydrazinecarbothioamidein ethanol and triethylamine yielded 2-(4-(1-(2-(4-(2-Arylhydrazono)-5-s-4,5-dihydrothiazol-2-yl)hydrazono)-ethyl)phenyl)isoindoline-1,3-dione and 2-(4-(1-(2-(5-(2-Arylhydrazono)-4-oxo-4,5-dihydrothiazol-2-yl)hydrazono)ethyl)-phenyl)isoindoline-1,3-dione.The reaction of 2-(4-(1-(2-(4-oxo-4,5-dihydrothiazol-2-yl)hydrazono)ethyl)phenyl)isoindoline-1,3-dione with arylidenemalononitrile also yielded 5-amino-2-(2-(1-(4-(1,3-dioxoisoindolin-2-yl)phenyl)ethylidene)hydrazinyl)-7-substituted-7H-pyrano[2,3-d]thiazole-6-carbonitrile. The structures of the newly synthesized compound were elucidated whenever possible on the basis of elemental analysis, spectral data, and alternative synthetic routes. Three of them were evaluated against a breast cancer cell line for their antitumor activity. CONCLUSIONS: Compound (1) has been shown to be useful in the synthesis of a new series of 1,3-thiazole, pyrano[2,3-d]thiazole and 4,5-dihydrothiazolo[4,5-b]pyridine derivatives using hydrazonoyl halides as precursors. The anticancer efficacy of compounds (9b), (9e), and (9f) against MCF-7, a breast cancer cell line, was also compared to the standard anticancer drug doxorubicin.

Utility of 5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide in the synthesis of heterocyclic compounds with antimicrobial activity.

BACKGROUND: Pyrazolines show different biological activities. In recent years, interest in the chemistry of hydrazonoyl halides has been renewed. 1,3,4-Thiadiazoles are one of the most common heterocyclic pharmacophores with a wide range of biological activities. RESULTS: Ethyl 2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methyl-thiazole-5-carboxylate, 2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one, and 1-(2-(5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-methylthiazol-5-yl)ethan-1-one were synthesized from the reaction of 5-(furan-2-yl)-3-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide with different halogenated compounds. Thiazole, 1,3,4-thiadiazole and pyrano[2,3-d]thiazole derivatives were also synthesized. The structures of the newly synthesized compounds were elucidated based on elemental analysis, spectral data, and alternative synthetic routes whenever possible. Additionally, the newly synthesized compounds were screened for antimicrobial activity against various microorganisms. CONCLUSIONS: A new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles, and pyrazoline-containing moieties were synthesized using hydrazonoyl halides as precursors and evaluated for their in vitro antibacterial, and antifungal activities. The antimicrobial results of the examined compounds revealed promising results and some derivatives have activities similar to the references used.

A facile synthesis, and antimicrobial and anticancer activities of some pyridines, thioamides, thiazole, urea, quinazoline, ß-naphthyl carbamate, and pyrano[2,3-d]thiazole derivatives.

BACKGROUND: Chalcones have a place with the flavonoid family and show a few very important pharmacological activities. They can used as initial compounds for synthesis of several heterocyclic compounds. The compounds with the backbone of chalcones have been reported to possess various biological activities. RESULTS: Pyridine and thioamide derivatives were obtained from the reaction of 3-(furan-2-yl)-1-(p-tolyl)prop-2-en-1-one with the appropriate amount of malononitrile, benzoylacetonitrile, ethyl cyanoacetate and thiosemicarbazide in the presence of ammonium acetate. The reaction of 3,5-di(furan-2-yl)-4,5-dihydro-1H-pyrazole-1-carbothioamide with ethyl 2-chloro-3-oxobutanoate, 3-chloropentane-2,4-dione or ethyl chloroacetate produced thiazole derivatives. Pyrano[2,3-d]thiazole derivatives were obtained as well from thiazolone to arylidene malononitrile. The structures of the title compounds were clarified by elemental analyses, and FTIR, MS and NMR spectra. Some compounds were screened against various microorganisms (i.e., bacteria +ve, bacteria -ve and fungi). We observed that compounds (3a), (4a), (4d), (5), (7) and compound (8) exhibited high cytotoxicity against the MCF-7 cell line, with IC50 values of 23.6, 13.5, 15.1, 9.56, 14.2 and 23.5 µmol mL-1, respectively, while compound (9) was displayed the lowest values against MCF-7 cell lines. CONCLUSIONS: Efficient synthetic routes for some prepared pyridines, pyrazoline, thioamide, thiazoles and pyrano[2,3-d]thiazole were created. Moreover, selected newly-synthesized products were evaluated for their antitumor activity against two carcinoma cell lines: breast MCF-7 and colon HCT-116 human cancer cell lines.

Synthesis of some new pyrazolo[1,5-a]pyrimidine, pyrazolo[5,1-c]triazine, 1,3,4-thiadiazole and pyridine derivatives containing 1,2,3-triazole moiety.

BACKGROUND: Pyrazolo[1,5-a]pyrimidines are purine analogues. They have beneficial properties as antimetabolites in purine biochemical reactions. This division compounds have attracted wide pharmaceutical interest because of their antitrypanosomal activity. RESULTS: The present work depicts an effective synthesis convention of pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]triazines, thieno[2,3-b]pyridines and polysubstituted pyridines containing 1,2,3,-triazole moiety from the reaction of sodium 3-(5-methyl-1-(p-toly)-1H-1,2,3-triazol-4-yl)-3-oxoprop-1-en-1-olate with the fitting heterocyclic amines and its diazonium salt, and active methylene compounds, individually. Likewise, thiazoles and, 1,3,4-thiadiazoles were obtained from 2-bromo-1-(5-methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethanone and some reagent such as hydrazonoyl chlorides and halo ketones. The newly synthesized compounds were established by elemental analysis, spectral data, and alternative synthetic route whenever possible. CONCLUSIONS: New series of pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]triazines, thieno[2,3-b]pyridines and polysubstituted pyridines containing the 1,2,3,-triazole moiety were synthesized via reactions of sodium 3-(5-methyl-1-(p-toly)-1H-1,2,3-triazol-4-yl)-3-oxoprop-1-en-1-olate with the appropriate heterocyclic amines and its diazonium salt. In addition, 1,3,4-thiadiazoles and, 1,3-thiazoles were acquired in a decent yield via the reaction of substituted thiourea with the appropriate hydrazonoyl chlorides and halogenated ketenes. Graphical abstract Synthesis of some new pyrazolo[1,5-a]pyrimidines, pyrazolo[5,1-c]triazines and thieno[2,3-b]pyridines.

Utility of 2-thioxo-pyrido[2,3-d]pyrimidinone in synthesis of pyridopyrimido[2,1-b][1,3,5]-thiadiazinones and pyridopyrimido[2,1-b][1,3]thiazinones as antimicrobial agents.

BACKGROUND: Pyridopyrimidines are of current interest because of their extensive variety of biological and pharmacological activities. RESULTS: A series of pyrido[2',3':4,5]pyrimido[2,1-b][1,3,5]thiadiazinones was obtained by aminomethylation of pyridopyrimidinethione with formaldehyde solution (37%) and different primary aromatic amines. Another series of pyrido[2',3:4,5]pyrimido[2,1-b][1,3]thiazinones was prepared by Michael addition reaction of pyridopyrimidinethione to the activated double bond of a number of arylidene malononitrile and 2-(benzo[d][1,3]dioxol-5-ylmethylene)malononitrile. The mechanisms of formation of the synthesized compounds were discussed and the assigned structure was established via microanalysis and spectral data (IR, 1H NMR, and Ms.). A comparative study of the biological activity of the synthesized compounds with chloramphenicol and trimethoprim/sulphamethoxazole is shown in Table 1. Generally, all synthesized compounds showed adequate inhibitory effects on the growth of Gram-positive and Gram-negative bacteria. CONCLUSIONS: In this study, we use a simple (synthetic) strategy for the synthesis of pyrimidothiadiazines, based on their aminomethylation through the Mannich reaction; they have also been synthesized by the application of the Michael addition to activated nitriles. Mechanisms and structures of the newly synthesized compounds were examined: the antimicrobial activity of some selected compounds was evaluated, which demonstrated adequate inhibitory effects. Graphical abstract The strategic structures of the products (7a-g).

Utility of 3-Acetyl-6-bromo-2H-chromen-2-one for the Synthesis of New Heterocycles as Potential Antiproliferative Agents.

Coumarin derivatives containing pyrazolo[1,5-a]pyrimidine, tetrazolo[1,5-a]pyrimidine, imidazo[1,2-a]pyrimidine, pyrazolo[3,4-d]pyrimidine, 1,3,4-thiadiazoles and thiazoles were synthesized from 6-bromo-3-(3-(dimethylamino)acryloyl)-2H-chromen-2-one, methyl 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)hydrazine carbodithioate, 2-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene) hydrazine carbothioamide and each of heterocyclic amine, hydrazonoyl chlorides and hydroximoyl chlorides. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Moreover, selected newly synthesized products were evaluated for their antitumor activity against a liver carcinoma cancer cell line (HEPG2-1). The results revealed that pyrazolo[1,5-a]pyrimidine 7c, thiazole 23g and 1,3,4-thiadiazole 18a (IC50 = 2.70 ± 0.28, 3.50 ± 0.23 and 4.90 ± 0.69 µM, respectively) have promising antitumor activity against liver carcinoma (HEPG2-1) while most of the tested compounds showed moderate activity.