First Synthesis for Bis-Spirothiazolidine Derivatives as a Novel Heterocyclic Framework and Their Biological Activity

2020 ◽  
Vol 20 (2) ◽  
pp. 152-160
Author(s):  
Eman M. Flefel ◽  
Walaa I. El-Sofany ◽  
Hanem M. Awad ◽  
Mahmoud El-Shahat
Keyword(s):  
Anticancer Activity ◽  
Thioglycolic Acid ◽  
Wide Spectrum ◽  
Heterocyclic Ring ◽  
Positive Control ◽  
Liver Carcinoma ◽  
Anticancer Activities ◽  
One Pot ◽  
Three Component Reaction ◽  
Synthetic Scaffold

Background: Spirothiazolidines are versatile synthetic scaffold possessing wide spectrum of biological interests involving potential anticancer activity. Objectives: To report the first synthesis of Bis Spiro-thiazolidine as a novel heterocyclic ring system. Method: One-pot three-component reaction including condensation of p-phenyllene diamine; cyclohexanone and thioglycolic acid produced Spiro-thiazolidine 4, which underwent further condensation with cyclohexanone and thioglycolic acid with equimolar ratio to introduce Bis-Spiothiazolidine 5 as the first synthesis. Also, bis spiro-thiazolidine arylidene derivatives 6-13 were synthesized by the reaction of Bis-Spiothiazolidine 5 with different aromatic benzaldehydes. Results: Four compounds 13, 12, 9 and 11 have shown highly significant anticancer activity compared to Doxorubicin® (positive control) against Human liver carcinoma (HepG2) and Human Normal Retina pigmented epithelium (RPE-1) cell lines. Conclusion: The novel bis-spirothiazolidine deriviatives have been synthesized for the first time and showed excellent anticancer activities compare with the corresponding spirothiazolidine derivatives.

scholarly journals Synthesis, Characterization and Cytotoxic Activity of New 2,9-BIS(2-Fluorobenzyl)-β-Carbolinium Bromide as a potential compound for anti-cancer agents

2019 ◽  
Vol 10 (SPL1) ◽  
Author(s):  
Mazlin Mohideen ◽  
Wan Mohamad Hafiz Wan Hamid ◽  
Nur Damia Zaidi ◽  
Adibah Akmal ◽  
Nuramanina Othman ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Synthesis Method ◽  
Positive Control ◽  
Crystallographic Analysis ◽  
Hep G2 ◽  
Anticancer Activities ◽  
One Pot ◽  
Recent Emergence ◽  
Anti Cancer ◽  
Ic50 Values

β-carbolines constitute a vast group of indole alkaloids and exhibit various biochemical effects and pharmacological properties. With the recent emergence of β-carboline in the field of cancer, this study investigated the synthesis, characterization, and potential anticancer activity of β-carboline derivative. An efficient method was described for the synthesis of new 2,9-bis(2-fluorobenzyl)-β-carbolinium bromide from L-tryptophan through the Pictet-Spengler reaction and oxidation of K2Cr2O7 by a sequential one-pot synthesis method then followed by N2, N9-benzylated using 2-fluorobezyl with good yield (92%). The structure of the compound was established by 1H-, 13C-NMR, and mass spectroscopy (ESI-MS) as well as single-crystal X-ray crystallographic analysis. The compound was tested for anticancer activity against Hela, HT-29, Hep-G2, and K562 cell lines by using MTT assay. 2,9-bis(2-fluorobenzyl)-β-carbolinium bromide exerted promising anticancer activities with IC50 values ranging between 0.97 to 6.00 μM as compared to doxorubicin which was employed as the positive control (0.77 μM). The results suggested that new, 2,9-bis(2-fluorobenzyl)-β-carbolinium bromide could potentially be developed as a novel anticancer agent.

scholarly journals Microwave Assisted Three Component Reaction Conditions to Obtain New Thiazolidinones with Different Heterocyclic Skeletons

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 38
Author(s):  
Fernando J. Lorenzo ◽  
Romina A. Ocampo ◽  
Sandra D. Mandolesi
Keyword(s):  
Microwave Irradiation ◽  
Thioglycolic Acid ◽  
Aldehyde Group ◽  
Green Solvent ◽  
Reaction Products ◽  
Reaction Conditions ◽  
One Pot ◽  
Microwave Assisted ◽  
Three Component Reaction ◽  
The One

We present here a new proposal for the “one pot” generation of new 4-thiazolidinones (9a–e) through a multicomponent reaction under microwave irradiation conditions, using aromatic and heteroaromatic amines (8a–e), absolute ethanol as a “green” solvent and modifying the aldehyde group in the glycosidic residue, synthesized from D-mannitol. The study is focused in the variation of the irradiation times and the concentration of thioglycolic acid in order to study the possibility of controlling the structure and/or stereochemistry of the products formed in the reaction. Thiazolidinones 9a–d were obtained with a 69–82% The generation of the corresponding reaction products were monitored by TLC and CG-MS, taking reaction aliquots. The conditions reaction proved to be chemoselective depending on the excess of acid and irradiation times.

scholarly journals Development of a Novel Series of Anticancer and Antidiabetic: Spirothiazolidines Analogs

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2511 ◽  
Author(s):  
Eman M. Flefel ◽  
Walaa I. El-Sofany ◽  
Reem A.K. Al-Harbi ◽  
Mahmoud El-Shahat
Keyword(s):  
Positive Control ◽  
The Other ◽  
Liver Carcinoma ◽  
Anticancer Activities ◽  
Alpha Amylase Inhibitor ◽  
Nitrogen Nucleophiles ◽  
Active Methylene ◽  
Alpha Glucosidase ◽  
Mcf 7

4-(4-Aminophenyl)-1-thia-4-azaspiro[4.5]decan-3-one 1 was prepared and allowed to react with nitrogen nucleophiles to give the corresponding hydrazones 2–4. Further, compound 1 underwent diazotization and afforded the parallel hydrazono derivative 5; moreover, compound 1 refluxed with active methylene derivatives yielded the corresponding aminospirothiazolo pyridine–carbonitrile derivative 6 and spirothiazolopyridinone–carbonitrile derivative 7. Condensation of spirothiazolidine 1 with 4-chlorobenzaldehyde gave the corresponding spiro arylidiene derivative 8, which was utilized as a component of Micheal addition to react with excess of nitrogen nucleophiles to yield novel ring frameworks 4-(3′-(4-chlorophenyl)–spiro [cyclohexane-1,5′-pyrazolo[3,4-d]thiazol]-6′(1′H)-yl)aniline (9) and 4-(3′-(4-chlorophenyl)-6′H- spiro[cyclohexane-1,5′-thiazolo[5,4-d]isoxazol]-6′-yl)aniline (10). Finally, when spirothiazolo pyridinone–carbonitrile derivative 7 sodium salt generated in situ was reacted with different alkyl halides, it produced the corresponding N-derivatives 12–16. Three compounds, 6, 14, and 16, showed high significantly anticancer activities compared with Doxorubicin® (positive control) against human breast carcinoma (MCF-7) and human liver carcinoma (HepG-2) cell lines. On the other hand, compounds 6 and 9 showed higher therapeutic indices for both of alpha-amylase inhibitor and alpha-glucosidase inhibitor than the other tested compounds compared with the antidiabetic Acarbose (positive control).

Effective Pharmacophore for CDC25 Phosphatases Enzyme Inhibitors: Newly Synthesized Bromothiazolopyrimidine Derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud El-Shahat ◽  
Mowafia A.M. Salama ◽  
Ahmed F. El-Farargy ◽  
Mamdouh M. Ali ◽  
Dalia M. Ahmed
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Enzyme Inhibitors ◽  
Wide Spectrum ◽  
Hct116 Cell ◽  
Cytotoxic Activities ◽  
The Novel ◽  
Anticancer Activities ◽  
Starting Compound

Background: Thiazolopyrimidine analogues are versatile synthetic scaffold possessing wide spectrum of biological interests involving potential anticancer activity. Objective: To report the synthesis of novel bromothiazolopyrimidine derivatives and the study of both molecular modeling and in-vitro anticancer activity. Method: Novel bromothiazolopyrimidine derivatives 5–18 have been prepared from 2-bromo-3-(4-chlorophenyl)-1-(3,4- dimethylphenyl)-propenone 3 as a key starting compound. The anti-cancer activities of the new compounds were evaluated against HepG2, MCF-7, A549 and HCT116 cell lines. Results: The compounds 16, 17 and 18 showed cytotoxic and growth inhibitory activities on both colon and lung cells. The cytotoxic activities of the novel synthetic compounds 8, 9, 11, 16, 17 and 18 were due to CDC25 phosphatases inhibition as shown by the enzymatic binding assay. Although compounds 8, 9 and 11 have only demonstrated CDC25B phosphatases inhibition. Conclusion: The novel bromothiazolopyrimidine derivatives showed promising in vitro anticancer activities against colon cancer HCT116 and lung cancer A549 cell lines comparable to the anticancer drug doxorubicin.

scholarly journals Acid Catalyzed Multicomponent One-Pot Synthesis of New Quinazolinone based Unsymmetrical C-N Linked Bis Heterocycles

2022 ◽  
Vol 34 (2) ◽  
pp. 432-436
Author(s):  
Nagamani Rayala ◽  
Sumathi Vodnala ◽  
Supriya Kamsani ◽  
A.K.D. Bhavani ◽  
Nagaraju Myakala ◽  
...  
Keyword(s):  
Hydrochloric Acid ◽  
13C Nmr ◽  
Aromatic Aldehydes ◽  
Catalytic Amount ◽  
Heterocyclic Ring ◽  
Spectroscopic Techniques ◽  
One Pot ◽  
Hybrid Compounds ◽  
Three Component Reaction ◽  
Acid Catalyzed

A novel series of unsymmetrical C-N linked bis heterocycles bearing quinazolinone and acridinedione skeletons have been synthesized in an acid promoted one pot multicomponent reaction. A blend of 6-aminoquinazolin-4-(3H)-one, aromatic aldehydes and cyclohexane-1,3-dione in a simple and efficient condensation-cyclization reaction using hydrochloric acid in catalytic amount as catalyst afforded unsymmetrical bis hybrids in good to excellent yields. Multiheterocyclic hybrid compounds were also synthesized using heterocyclic ring containing aldehyde in three component reaction. The synthesized quinazolinone-acridindione hybrids were characterized using spectroscopic techniques such as a IR, 1H NMR, 13C NMR, ESI-mass and HRMS.

scholarly journals Synthesis and antitumor activities of novel Mannich base derivatives derived from natural flavonoids

2021 ◽  
Author(s):  
Huma Bhatti ◽  
Rubina Rubina ◽  
Faisal Rashid ◽  
Sumera Zaib ◽  
Jamshed Iqbal ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Mannich Base ◽  
Mannich Bases ◽  
Spectroscopic Techniques ◽  
Antitumor Activities ◽  
Dapi Staining ◽  
One Pot ◽  
Through Flow ◽  
Three Component Reaction ◽  
Apoptotic Effect

In our current study, a series of reactions with isolated natural flavonoids (2-phenylchromen-4-one) and flavanone (2,3-dihydro-2-phenylchromen-4-one) through Mannich base was carried out by a one-pot three-component reaction. Their structure-activity relationship study (SAR) reveals the anticancer activity of natural compounds and their Mannich bases. The flavones were substituted by imine at position C-8, while in the flavanones, the reaction takes place at positions C-8 and C-3. Spectroscopic techniques characterized all the isolated and newly synthesized derivatives. Anticancer activity was checked on HeLa and MCF-7 (cancer cell lines) and BHK-21 (normal cell line). Using propidium iodide (PI) and DAPI staining as fluorescence microscopic imaging was confirmed the Apoptotic effect of potent compound. Further, it was evaluated by cell cycle analysis through flow-cytometry, reactive oxygen species and lactate dehydrogenase production. The caspase-9 and -3 activity were estimated by mitochondrial membrane potential. Derivative of naringenin, ((2S)-4′,5,7-Trihydroxyflavan-4-one) where reactions occur at position C-3 were active than others.

Fe3O4@SiO2-Propyl covalented dapsone-copper complex: Synthesis, characterization and application for the synthesis of new derivatives of azo-linked thiazolidinones and their solvatochromism evaluation

2021 ◽  
Vol 17 ◽  
Author(s):  
Leila Zare Fekri
Keyword(s):  
Electron Microscopy ◽  
Thioglycolic Acid ◽  
Biological Activities ◽  
Solvent Free ◽  
Gravimetric Analysis ◽  
One Pot ◽  
Free Condition ◽  
Solvent Free Condition ◽  
Three Component Reaction ◽  
Derivatives Of

Background: Thiazolidinone-4-ones belong to an important heterocyclic compounds because of their broad spectrum of biological activities. Several methods for the synthesis of 4-thiazolidinones were reported in the literature. The main synthetic routes to synthesize 1,3-thiazolidin-4-ones is the three component reaction between amine, a carbonyl compound and a mercapto-acid. Objective: Dapsone-Cu supported on silica coated Fe3O4 (Fe3O4@SiO2-pr@dapsone-Cu) as a new heterogeneous nanoparticle catalyst was synthesized and the structure and morphology of this catalyst were characterized by Fourier transform infrared spectroscopy (FT-IR), Xray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), zeta potential, vibrating sample magnetometry (VSM) and thermal gravimetric analysis (TGA). The new synthesized catalyst was applied as an effective nanocatalyst for the synthesis of new derivatives of azo-linked thiazolidinones through one-pot multi-component reaction of various aromatic aldehydes, thioglycolic acid and 4-aminoazobenzene under solvent-free condition. Methods: A mixture of aldehyde, thioglycolic acid, 4-aminoazobenzene (1 mmol) and 0.05 g Fe3O4@SiO2@dapsone-Cu MNPs were stirred at room temperature under solvent-free condition. Results: We report a facile, green, new and efficient method for the synthesis of thiazolidine-4-ones through three component reaction of various aldehydes, thioglycolic acid and 4-aminoazobenzene in the presence of Fe3O4@SiO2-propyl@dapsone-Cu complex under solvent-free reaction. Conclusion: This new procedure has the notable advantages such as excellent yields, short reaction time, operational simplicity, easy work-up, eco-friendly and using a non-toxic catalyst. Also, the catalyst is easily recoverable in the presence of an enourmous magnet and reused for six consecutive reaction cycles without significant loss of activity.

Synthesis of novel 1,4-disubstituted 1,2,3-triazolo-bosentan derivatives – evaluation of antimicrobial and anticancer activities and molecular docking

RSC Advances ◽  
2015 ◽  
Vol 5 (127) ◽  
pp. 105266-105278 ◽  
Author(s):  
K. Easwaramoorthi ◽  
A. Jeya Rajendran ◽  
K. Chennakesava Rao ◽  
Y. Arun ◽  
C. Balachandran ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Activities ◽  
One Pot ◽  
One Pot Synthesis

One pot synthesis with good yields. Good antimicrobial activity against 4EMV receptor. Prominent anticancer activity against A549 and SKOV-3 cell lines. Significantin vitrocytotoxicity at 7.81 μg mL−1. Docking mode of1hwith 2XP2 receptor.

One-Pot Three-Component Synthesis and Molecular Docking of Some Novel 2-Thiazolyl Pyridines as Potent Antimicrobial Agents

2019 ◽  
Vol 19 (6) ◽  
pp. 527-538 ◽  
Author(s):  
Fathy M. Abdelrazek ◽  
Sobhi M. Gomha ◽  
Mohamed E.B. Shaaban ◽  
Kamal A. Rabee ◽  
Heba N. El-Shemy ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Binding Affinities ◽  
Thiazole Derivatives ◽  
One Pot ◽  
Three Component Reaction

Background: Thiazoles and pyridines are versatile synthetic scaffolds possessing wide spectrum of biological effects including potential antimicrobial activity. Objective: In the efforts to develop suitable antimicrobia drugs, medicinal chemists have focused on thiazole derivatives. A novel series of 2-thiazolyl pyridines was prepared in a one-pot three-component reaction using 2-bromoacetyl pyridine as a starting precursor. Method: Structure of the synthesized compounds was elucidated by spectral data (FT-IR, 1H NMR, 13C NMR, and mass) and elemental analyses. The prepared compounds were screened for their in vitro antimicrobial activity. Results: The results revealed that compounds 4a,b,e-g and 12 showed promising activity. Molecular docking studies using MOE software were carried out for compounds 4a and 4b which exhibited potent activities indicated by the diameter zones (4a; 3.6, 4.0, 1.2 mm) (4b; 4.2, 3.5, 1.5 mm) and the binding affinities (4a; -5.7731, -5.3576, -4.6844 kcal mol-1) (4b; -5.9356, -2.8250, -5.3628 kcal mol-1) against Candida albicans, Bacillus subtilis and Escherichia coli, respectively. Conclusion: This paper describes a facile and efficient MCR for synthesis of 2-thiazolyl pyridines from reaction of 2-bromoacetyl pyridine with different reagents. There was an agreement between the values of binding affinities and interactions and the data obtained from the practical antimicrobial screening of the tested compounds.

Arylhydrazono/Aryldiazenyl Pyrazoles: Green One-Pot Solvent-Free Synthesis and Anticancer Evaluation

2020 ◽  
Vol 17 (10) ◽  
pp. 772-778
Author(s):  
Abdulrhman Alsayari ◽  
Abdullatif Bin Muhsinah ◽  
Yahya I. Asiri ◽  
Jaber Abdullah Alshehri ◽  
Yahia N. Mabkhot ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Binding Mode ◽  
Docking Studies ◽  
Solvent Free ◽  
Pyrazole Derivatives ◽  
One Pot ◽  
Solvent Free Conditions ◽  
Hybrid Molecules

The aim of this study was to synthesize and evaluate the biological activity of pyrazole derivatives, in particular, to perform a “greener” one-pot synthesis using a solvent-free method as an alternative strategy for synthesizing hydrazono/diazenyl-pyridine-pyrazole hybrid molecules with potential anticancer activity. Effective treatment for all types of cancers is still a long way in the future due to the severe adverse drug reactions and drug resistance associated with current drugs. Therefore, there is a pressing need to develop safer and more effective anticancer agents. In this context, some hybrid analogues containing the bioactive pharmacophores viz. pyrazole, pyridine, and diazo scaffolds were synthesized by one-pot method. Herein, we describe the expedient synthesis of pyrazoles by a onepot three-component condensation of ethyl acetoacetate/acetylacetone, isoniazid, and arenediazonium salts under solvent-free conditions, and the evaluation of their cytotoxicity using a sulforhodamine B assay on three cancer cell lines. Molecular docking studies employing tyrosine kinase were also carried out to evaluate the binding mode of the pyrazole derivatives under study. 1-(4-Pyridinylcarbonyl)-3- methyl-4-(2-arylhydrazono)-2-pyrazolin-5-ones and [4-(2-aryldiazenyl)-3,5-dimethyl-1H-pyrazol-1- yl]-4-pyridinylmethanones, previously described, were prepared using an improved procedure. Among these ten products, 1-isonicotinoyl-3-methyl-4-[2-(4-nitrophenyl)hydrazono]-2-pyrazolin-5-one (1f) displayed promising anticancer activity against the MCF-7, HepG2 and HCT-116 cell lines, with an IC50 value in the range of 0.2-3.4 μM. In summary, our findings suggest that pyrazoles containing hydrazono/ diazenyl and pyridine pharmacophores constitute promising scaffolds for the development of new anticancer agents.

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