Syringaldehyde as a scaffold for the synthesis of some biologically potent heterocycles

Syringaldehyde was utilized in synthesis of different heterocyclic systems. Some of the synthesized compounds 2 , 7 , 8 , 10 , 11 , and 13 were tested for antioxidant activity where they showed ability to inhibit oxidation in kidney and rat brain homogenates using 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Also, the activity against cancer was examined using the standard MTT method for two human tumor cell lines namely; mammary gland breast cancer MCF-7 and hepatocellular carcinoma HepG2. The highest activity as antioxidant and antitumor agents was exhibited by compounds 8 and 11 . However, moderate activities were shown by compounds 10 and 13 . While, compounds 2 , 7 showed weak activities.     

Utilization of 2(3H)‐Furanone Bearing a Pyrazolyl Side Chain for the Construction of a Variety of Thiazolidinone Derivatives

2(3H)‐Furanone 1 was utilized for the construction of thiazolidinone derivatives. Thus, upon treatment the cyano derivatives 5 with thioglycolic acid afforded the thiazolidinone derivatives 6 . Reaction of the Schiff base derivative 9 with thioglycolic acid gave the thiazolidinone derivative 10 . Decomposition of the azides 11 in dry benzene in the presence of thioglycolic acid gave the thiazolidindione derivative 12 . Antimicrobial activities of synthesized compounds were tested. Some of the tested compounds showed promising activities.     

Synthesis,PM3‐Semiempirical,and Biological Evaluation of Pyrazolo[4,3‐c]quinolinones

A series of α,β‐unsaturated ketones containing quinolone moieties 2 , 3 , 4 , 5 , 6 were synthesized by condensation of 7‐methoxyquinoline‐2,4(1H,3H)‐dione ( 1 ) with different aryl aldehydes. Pyrazole derivatives 8 , 9 , 10 , 11 were also synthesized via refluxing of α,β‐unsaturated ketones 2 , 3 , 4 , 5 , 6 with hydrazine derivatives. Newly synthesized compounds were characterized by elemental analyses, spectral data, and screened for their antioxidant and antitumor activities. Geometrical optimizations of the molecular structures for different synthesized compounds were studied.     

Microwave assisted synthesis of some new heterocyclic spiro-derivatives with potential antimicrobial and antioxidant activity

Homophthalic anhydride reacts with different aromatic amines to produce N-substituted homophthalimides. Bromination of the latter produces 4,4-dibromo-homophthalimide derivatives that can be used as precursors for spiro-derivatives. The dibromo derivatives react with different binucleophilic reagents to produce several spiro-isoquinoline derivatives. Reaction of the dibromo derivatives with malononitrile produces dicyanomethylene derivatives which react with different binucleophiles to produce new spiro-derivatives. Structures of the newly synthesized compounds are proved using spectroscopic methods such as IR, 1H-NMR and 13C-NMR. The newly synthesized compounds were tested for their antimicrobial and antioxidant activities, showing weak or no antimicrobial activity. On the other hand select compounds showed promising antioxidant activities.     

Utility of Hantzsch Ester in Synthesis of Some 3,5‐Bis‐dihydropyridine Derivatives and Studying Their Biological Evaluation

The present work involves synthesis of new 3,5‐bis‐substituted dihydropyridine derivatives 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 starting from dihydropyridine‐3,5‐dicarboxylate ( 1 ) as starting material. Structures of new compounds were established by spectral and elemental analyses. Some of the new compounds were evaluated for anticancer and antimicrobial activity. Screening data of the tested compounds show promising anticancer and antimicrobial activity. The detail synthesis, spectroscopic data, and pharmacological activities are reported.     

Synthesis and Computational Analysis of New Antioxidant and Antimicrobial Angular Chromenopyrimidines

A convenient synthetic protocol for the synthesis of novel chromenopyrimidine derivatives based on angular scaffold has been developed from the readily available enaminonitrile precursor 1 . The skeleton of chromenopyrimidines has been decorated with different moieties in order to approach compounds with improved antioxidant and antimicrobial activities. Compound 1 was reacted with Ac₂O to yield benzochromenopyrimidine 6 that gave chloropyrimidine 7 via chlorination reaction. The reaction of chloropyrimidine 7 with different amines afforded a series of benzochromenopyrimidines 9 – 12 . The hydrazine 11 and hydrazide 13 derivatives showed excellent antioxidant activity in addition to the potent antimicrobial activity revealed by aminopyrimidines 10 and 16 . Computational docking studies indicated the potential recognition of compound 13 towards antioxidant binding site. Dual evaluations of the antimicrobial affinity of compound 16 indicated its promising activity as antimicrobial lead.     

Design,synthesis of new pyrimidine derivatives as anticancer and antimicrobial agents

A new series of 6-aryl-5-cyano thiouracil derivatives were synthesized. Cyanouracil 1 was condensed with monochloroacetic acid and different aldehydes to give thiazolopyrimidine 2. On the other hand, treatment of cyanouracil 1 with 2-chloro-N-substituted-phenylac etamide afforded 4. Hydrazinolysis of 6 afforded the hydrazino derivatives 7 which upon reaction with different electrophilic reagents such as acetic anhydride, benzoyl chloride, and carbon disulfide yielded pyrimidine derivatives 8–15. Some of the new derivatives were explored for their antimicrobial activities. Compounds 7 and 9 have a promising activity, relatively equipotent to the reference drug. All of the new synthesized compounds were tested in vitro for their antiproliferative activities against HePG-2 and MCF-7 cell lines. Compounds 7, 9, and 2d displayed potent growth inhibitory effect toward the two cell lines more than the standard drug 5-FU. Furthermore, a docking study of the most active compounds was performed with thymidylate synthase enzyme.     

Synthesis and Reactions of Some Novel Nicotinonitrile,Thiazolotriazole, and Imidazolotriazole Derivatives for Antioxidant Evaluation

The novel 2-(1H)-pyridone, the lead compound of the pyridone derivative 1, reacted with an electrophilic reagent (ethyl chloroacetate) to give the corresponding ester 2. Condensation of compound 2 with thiosemicarbazide and/or hydrazine hydrate afforded the mercaptotriazole and the corresponding acetic acid hydrazide derivatives 3 and 4, respectively. The latter compound reacted with ethyl acetoacetate, ethyl cyanoacetate, and maleic anhydride to give compounds 5, 6, and 7, respectively. Alkylation of compound 3 with methyl iodide or chloroacetic acid afforded methylsulfanyltriazole and thiazolotriazole derivatives 8 and 9, respectively. Compound 8 reacted with glycine to afford the imidazotriazole derivative 10. Both compounds 9 and 10 reacted with glucose and benzaldehyde to give compounds 11, 12, 13, and 14, respectively. Some of the prepared products were selected and subjected to screening for their antioxidant activity.     

Synthesis and antioxidant activities of flavonoids derivatives, troxerutin and 3’, 4’, 7-triacetoxyethoxyquercetin

Syntheses of two very important derivatives of quercetin,troxerutin and 3’,4’,7-triacetoxyethoxyquercetin were described.The latter was synthesized by highly selective esterification reaction in first time.The compounds were characterized by NMR,IR and Mass spectroscopy.Additionally,the antioxidant activities of the compounds were tested by means of improved pyrogallol autoxidation method.This was the first in using this method to test the antioxidant activities of these two compounds in vitro.The optimum system of pyorgallol autoxidation spectrophotometry was investigated and established according to the reaction rules.The assay indicated that these compounds showed noticeable antioxidant activities,and compound 2 was much more effective as a free radical scavenger than the compound 1 vitamin C was used as a reference material.     

Microwave assisted synthesis of some new thiazolopyrimidine, thiazolodipyrimidine and thiazolopyrimidothiazolopyrimidine derivatives with potential antioxidant and antimicrobial activity

Biginelli reaction of ethyl acetoacetate, thiourea and the appropriate aromatic aldehyde was used to produce ethyl 4-aryl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylates, that reacted with bromomalononitrile to give ethyl 3-amino-5-aryl-2-cyano-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylates rather than the isomeric 7H-thiazolo[3,2-a]pyrimidines. Thiazolopyrimidine derivatives reacted with carbon disulphide to yield ethyl 9-aryl-7-methyl-2,4-dithioxo-2,3,4,9-tetrahydro-1H-thiazolo[3,2-a:4,5-d']dipyrimidine-8-carboxylates, that reacted with phenacyl bromide to produce ethyl 8-methyl-10-(4-methoxyphenyl)-3-substituted-5-thioxo-2(un)subatituted-10H-thiazolo[3',2':1',2']pyrimido[4',5':4,5]thiazolo[3,2-a]pyrimidine-9-carboxylates. The aforementioned reactions were carried out using both conventional chemical methods and with the assistance of microwave irradaition. Comparison between both methods showed that the microwave assisted method is preferable because of the time reduction and yield improvements achieved. The new compounds were tested for their biological activity as antioxidants, antibacterial or antifungal agents. Some of the new compounds were found to have moderate to good antioxidant and antimicrobial activities.     

Antibacterial, Antiurease, and Antioxidant Activities of Some Arylidene Barbiturates

Some series of arylidene barbiturates and thiobarbiturates were evaluated for their antibacterial, antioxidant, and urease inhibition activities. The arylidene barbiturates and thiobarbiturates were tested for antimicrobial activity using the agar well diffusion technique against 13 bacteria. The synthesized compounds (1a–g) were screened for antiurease and antioxidant activities. The results showed that the synthesized compounds (1a–g) had effective antiurease, antioxidant, and antibacterial activities.     

Synthesis of Various Nitrogen Heterocycles as Antimicrobial Surface Agents

A number of novel, thiazole 5 , oxadiazole 6 , thiadiazole 7 , triazole 8 , 9 , and fused triazole derivatives 10 , 11 , 12 were obtained from a valuable and inexpensive fatty acids (stearic acid). Propoxylation of these compounds using 5 moles of propylene oxide produced nonionic surface active agents ( 13 , 14,15 16 , 17,18,19,20 ). The surface properties and the biodegradability of the latter compounds were evaluated. Some of the synthesized compounds were investigated for their antimicrobial activities.     

Synthesis and Antimicrobial Activity of Some Novel Substituted Bis‐Pyridone,Pyrazole, and Thiazole Derivatives

A variety of novel bis‐heterocyclic derivatives were synthesized via the reaction of bis‐cyanoacetanilide derivative 3 with various aromatic aldehydes (1:2 molar ratio), to give the corresponding bis‐arylidene derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m . On the other hand, reacting compound 3 with substituted 2‐hydroxybenzaldehydes 6a , 6b , 6c afforded 2‐iminochromene‐3‐carboxamides 7a , 7b , 7c . The reaction of compound 5 with malononitrile afforded the novel bis‐pyridones 9a , 9b , 9c , 9f , 9g , 9h . The reaction of 5 with hydrazine derivatives afforded pyrazoles 11a , 11b , 11c , 11d , 11e , 11f , respectively. Compound 3 reacts with phenyl isothiocyanate in the presence of potassium hydroxide at room temperature followed by addition of some different halo‐carbonyl compounds to afford bis‐poly‐functionalized thiazole derivatives 13a , 13b , 13c . The bis‐enamine derivative 15 reacts also with hydrazine hydrate, guanidine, and hydroxylamine to give bis‐pyrazole 17 , pyrimidine 19 , and isoxazole 21 derivatives, respectively. Some of the newly synthesized compounds show moderate to high antimicrobial activity.     

Synthesis and evaluation of novel 4H-pyrazole and thiophene derivatives derived from chalcone as potential anti-proliferative agents,Pim-1 kinase inhibitors,and PAINS

The chalcone derivatives 3a-d reacted with either malononitrile or ethyl cyanoacetate in ethanol in the presence of catalytic amount of ammonium acetate in an oil bath at 120°C to give the Knowevenagel condensation products 5a-h . The latter compounds reacted with hydrazine hydrate and afforded the 4H-pyrazole derivatives 7a-h , respectively. The reaction of compounds 7a-h with ethyl cyanoacetate in dimethylformamide under refluxing condition afforded the cyanoacetamido derivatives 8a-h , respectively. When compounds 8a-h reacted with elemental sulfur and either of malononitrile or ethyl cyanoacetate in ethanol containing triethylamine, the thiophene derivatives 9a-h and 10a-h , respectively, were obtained. The structure of the newly synthesized compounds was established by the analytical and spectral data. All the newly synthesized compounds were evaluated against the six cancer cell lines: A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. Compounds 3c , 5h , 7g , 7h , 8f , 9e , 9g , and 10g were selected to examine their Pim-1 kinase inhibition activity as these compounds showed high inhibition toward the c-Met kinase and the tested cancer cell lines. Furthermore, compounds 3b , 3c , 5g , 5h , 7f , 7g , 7h , 8e , 8f , 8g , 8h , 9e , 9f , 9g , 9h , 10g and 10h were selected to be tested for pan-assay interference compounds analysis (PAINS). Almost all the tested compounds showed zero PAINS alert and can be used as drug compounds in the future.     

Dodecanoyl isothiocyanate and N′-(2-cyanoacetyl) dodecanehydrazide as precursors for the synthesis of different heterocyclic compounds with interesting antioxidant and antitumor activity

Dodecanoyl isothiocyanate 1 was utilized for the construction of thioureido, 2-thioxo-2,3-dihydroquinazolin-4(1H)-one, benzo[d]-1,3-thiazin-4(H)-one and 3-amino quinazolin-4(3H)-one derivatives 2, 3, 4, and 5 respectively. However, N′-(2-cyanoacetyl) dodecanehydrazide 6 was also used as a key starting material for the construction of a variety of new pyrazolone, pyrazole, thiadiazole, pyridazine, chromeno[2,3-c]pyrazole, and dithiolane derivatives 7, 9, 12, 15, 18, and 20, respectively. The newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H NMR, and mass spectra). Some of the newly synthesized compounds bearing heterocyclic moieties were tested for antioxidant activity as reflected in their ability to inhibit oxidation in rat brain and kidney homogenates using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) inhibition. Also, in vitro anticancer activity was examined using the standard (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) (MTT) method against a panel of two human tumor cell lines namely; hepatocellular carcinoma HepG2 and mammary gland breast cancer MCF-7. Compounds 12 and 16b exhibited the highest activities as antioxidant and antitumor agents. Meanwhile, compounds 7 and 20 showed moderate activities and the rest of the tested compounds showed weak activities.     

Synthesis and biological assessment of some fused Pyran derivatives

Pyran was formed by reacting methyl 3-methoxyacrylate (1) with 2-benzylidenemalanonitrile to form compound 2 . The pyrano derivatives 3–6 were obtained by reacting the second molecule with 2-benzylidenemalanonitrile, carbon disulfide, formamide, and benzylidene cyclohexanone. Compound (2) interacted with ethyl chloroacetate to form compound 8 , which then cyclized in the presence of sodium ethoxide to form compound 9 . Compound 7 was formed when compound (2) was treated with acetic acid in the presence of sulfuric acid and reacted with ethylchloroacetate to form compound 10 and then was converted to compound 11 by the addition of sodium ethoxide. Analytical and spectral data have been used to determine the structures of the newly synthesized substances and they were then tested for their antibacterial and antioxidant activities. In terms of antioxidant activity, compounds 2 and 8 were found to have the greatest and lowest levels, respectively, against Enterobacter aerogenes.     

Synthesis,characterization, antioxidant and antibacterial properties of non-peripherally and peripherally tetra-substituted phthalocyanines

abstract

This study focuses on the synthesis, spectral, antioxidant and antibacterial properties of the metal-free, zinc and cobalt phthalocyanines (3–8) bearing 4-methoxy-phenoxy substituents on the nonperipheral [(1(4), 8(11), 15(18), 22(25)] or peripheral [2(3), 9(10), 16(17), 23(24)] positions. The new synthesized complexes 7 and 8 have been characterized by elemental analysis, FT-IR, MALDI-MS, and UV-vis spectral data. The antioxidant activities of all tested compounds were investigated by applying three different antioxidant methods such as radical scavenging ability of 1,1-diphenyl-2-picrylhydrazyl, chelating ability to ferrous ions and reducing power activity methods. In addition, the antibacterial activities of the compounds were screened by disc diffusion method against one gram-negative and four gram-positive bacteria. The tested phthalocyanine compounds showed very good antioxidant activity and promising antibacterial properties.     

1,2,7,9-四取代去氢骆驼蓬碱衍生物的合成及体外抗肿瘤活性

为了寻找高效低毒的抗肿瘤候选化合物, 以去氢骆驼蓬碱为原料, 对β-咔啉环的2-,7-和9-位3个结构位点进行了结构改造, 合成了11个去氢骆驼蓬碱衍生物, 化合物的结构经核磁共振、 红外光谱、 质谱及元素分析确证. 采用四甲基偶氮唑盐(MTT)法初步测试了目标化合物体外抗肿瘤(Bel-7402, 786-0, BGC-823, A375, 769-P和MCF7)活性, 结果表明化合物4a, 4b, 8a和8b具有显著的体外抗肿瘤活性.     

Design,Synthesis, Molecular Docking,and Evaluation Antioxidant and Antimicrobial Activities for Novel 3-phenylimidazolidin-4-one and 2-aminothiazol-4-one Derivatives

On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs (1–11) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6, respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p-nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8, 9, 10, and 11, respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.     

吲哚马来酰亚胺类化合物的合成及其抗肿瘤活性

为寻找具有抗肿瘤活性的新化合物, 设计合成吲哚马来酰亚胺类化合物, 并评价其体外抗肿瘤活性. 以吲哚与2-氯乙酰胺为起始原料, 经取代、缩合等反应合成了单吲哚马来酰亚胺衍生物5a～5t, 以5-硝基吲哚和不同的N-(3-氯丙基)叔胺经取代、还原、缩合等反应得到了双吲哚马来酰亚胺衍生物9a～9f. 共合成了26个未见文献报道的新化合物, 其结构经质谱、元素分析和核磁共振氢谱确证. 采用MTT法, 测试了目标化合物对肿瘤细胞株HL60, ECA-109, A549, SMMC-7721和PC-3的增殖抑制活性, 结果表明部分化合物对所测肿瘤细胞株均显示一定的抑制作用.