A simple and versatile protocol for the preparation of functionalized heterocycles utilizing 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione

The reaction of ethyl benzoylpyruvate with phenyl isothiocyanate in alkaline medium yields 4-benzoyl-5-phenylamino-2,3-dihydrothiophene-2,3-dione (1). Reaction of the intermediate 1 with primary aromatic amines such as aniline derivatives, benzidine and secondary aliphatic amines, namely diethylamine, piperidine, morpholine and piperazine afforded the corresponding thiophene 2a–2g and amide 3a–3d derivatives. Compound 1 reacts with N,N′- and N,O-dinucleophiles such as 1,2-diaminoalkanes, 2-aminoethanol, 1-aminoguanidine, guanidine, urea, 1,2-phenylenediamine and 2-amino-4-methylphenol to form the heterocylic compounds 4–10.     

5-Pyrenylidene-hydantoin, 2-thiohydantoin derivatives: synthesis,S- and N-alkylation

5-Pyrenylidene-2-thiohydantoin derivatives 2a–d were prepared by condensation of pyrene-1-carboxaldehyde with 2-thiohydantoin derivatives. Compounds 2a,b undergo Mannich reaction with formaldehyde and morpholine to give the corresponding Mannich products 3a,b respectively. S- and N-monoalkyl-5-pyrenylidene-hydantoin derivatives 5a,b and 6a,b were prepared by reaction of 5-pyrenylidene-2-thiohydantoin sodium salts with 1,3-dioxolan-methylsulfate derivatives. Deprotection of the products afforded 5-pyrenylidene-hydantoin (7), S- and N-dihydroxy derivatives 8a,b and 9a,b respectively. Reaction of 2a with methyl iodide afforded the corresponding S-methyl derivative 10, which reacted with secondary amines such as morpholine and piperidine afforded the glycocymidine derivatives 11a,b. Reaction of 2a with (2,3,4,6-tetra-O-acetyl-α-? D-glucopyranosyl)bromide afforded a mixture of S- and N-glucoside derivatives 12 and 13 respectively. Deprotection of 12 afforded compound 7, while deprotection of 13 furnished 5-Pyrenylidene-3-? D-glucopyranosyl-2-thiohydantoin (14). Reaction of 7 with propargyl chloride in DMF afforded the monoalkynyl- and bis-alkynyl-hydantoin derivatives 15 and 16, respectively. Reaction of 15 with p-bromophenyl-ether derivative 17 yielded the bis-alkynyl derivative 18.     

Synthesis and antimicrobial evaluation of some pyrazolo-thiazolyl alkoxy-1H-isoindole-1, 3(2H)-dione derivatives

1,3-Thiazolidine-2,4-dione 2 has been synthesized by the cyclisation reaction of thiourea and chloroacetic acid in the presence of ethanol. The reaction of compound 2 with substituted aromatic aldehyde afforded the corresponding derivatives of substituted 5-benzylidene-1,3-thiazolidinone-2,4-dione 3a–d, which upon reflux with ω-bromoalkoxyphthalimide gave 2-{[-5-(substituted benzylidine)-2,4-dioxo-1,3-thiazolidine-3-yl]alkoxy} -1H-isoindole-1,3(2H)-dione 4a–i. Further, compounds 4a–i were treated with phenyl hydrazine and 2,4 dinitro phenyl hydrazine in the DMF to yield the title compound 2-[5-oxo-2,3-substituted diphenyl-2H-pyrazolo[3,4-d][1,3]thiazol-6(5H)-yl)alkoxy]-1H-isoindole-1,3(2H)-dione 5a–r. Structures of newly synthesized compounds were established based on elemental analysis, IR, ¹H NMR and mass spectral data. Synthesized compounds have been assayed for their antibacterial activities against B. subtilis, K. pneumoniae, P. aeruginosa and S. aureus and antifungal activities against A. fumigatus and C. albicans.     

Study of Biological Activities and ADMET-Related Properties of Novel Chlorinated N-arylcinnamamides

A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2E)-N-[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1. (2E)-N-[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2E)-3-(3,4-dichlorophenyl)-N-[3-(trifluoromethyl)phenyl]prop-2-enamide, (2E)-3-(3,4-dichloro- phenyl)-N-[4-(trifluoromethyl)phenyl]prop-2-enamide and (2E)-3-(3,4-dichlorophenyl)- N-[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum, M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.     

The synthesis,antimicrobial activity and absorption characteristics of some novel heterocyclic disazo dyes

Aniline derivatives were diazotized and coupled with 3-aminocrotononitrile to give the corresponding 2-arylhydrazono-3-ketiminobutyronitriles. Cyclization of these arylhydrazono derivatives with hydrazine monohydrate afforded 5-amino-4-arylazo-3-methyl-1H-pyrazoles which were subsequently diazotised and coupled with malononitrile to yield a series of pyrazolylhydrazonomalononitriles. These compounds were then reacted with hydrazine monohydrate to provide 10, novel, heterocyclic disazo dyes, which were characterized by elemental analysis and spectral methods. The antimicrobial activity and absorption characteristics of the dyes were also examined in detail.     

Synthesis of some new fused thiopyrano[2,3-d]thiazoles and their derivatives

A series of some new fused thiopyrano[2,3-d]thiazole derivatives have been synthesized by a stereo-selective hetero-Diels-Alder reaction of 5-(2,4-dihydroxy-benzylidene)-4-thioxo-thiazolidine derivatives 3a,b with acrylonitrile, ethyl acrylate, N-phenylmale-imide, ω-nitrostyrene and N-phenyl-1, 3, 4-triazole-2,5-dione. 5-Amino-9-hydroxy-dihydro-benzopyrano[3′,4′:4,5]thiopyrano[2,3-d]thiazol-6-one derivatives 14a,b have been synthesized by Michael addition of 3a,b with malononitrile. Structures and conceivable mechanisms are discussed.     

Synthesis and application of some new oxazole derivatives as antimicrobial agents

5-(p-Acetylphenyl)-2-phenyloxazole ( I ) was condensed with aromatic aldehydes to furnish chalcones 2a-e . Cyclocondensation of 2a-e with hydrazine hydrate and with phenyl hydrazine led to the formation of pyrazoline derivatives 3a-e and 4a-e respectively. Similarly, 2a was interacted with hydroxylamine to give isoxazoline ( 5 ). On the other hand, condensation of 1 with phenyl hydrazine yielded hydrazone 6 which on treatment with Vilsmeier reagent (DMF/POCl₃) gives 5-[p-(4-formyl-1-phenylpyrazol-3-yl)phenyl]-2-phenyloxazole ( 7 ). Also, a few derivatives of 7 have been prepared. Moreover, all compounds were screened for their antimicrobial activity against some strains of bacteria and fungi.     

Ketene N,S-acetals in heterocyclic synthesis: Part 1: Synthesis of N-phenyl-2-ylidene and 2,5-diylidene-4-thiazolidinone derivatives

Ketene N,S-acetal potassium salts (2a–g), prepared via reaction of active methylenes (1a–g) with phenyl isothiocyanate in the presence of potassium hydroxide, were allowed to react with ethyl chloroacetate or chloroacetamide to afford the corresponding 2-ylidene-4-thiazolidinones (3a–g) in good yields. Compounds (3a–g) reacted with a variety of aromatic aldehydes to afford the corresponding 5-arylidene-2-ylidene-4-thiazolidinone derivatives (10a–e). Reaction of compound (3a) with triethylorthoformate afforded 5-ethoxymethylene-2-ylidene-4-thiazolidinone derivative (7), which was allowed to react with ammonia or phenyl hydrazine to give the corresponding enamino or hydrazino derivatives (8a) or (8b), respectively.     

Synthesis and characterization of coumarin thiazole derivative 2-(2-amino-1,3-thiazol-4-yl)-3H-benzo[f]chromen-3-one with anti-microbial activity and its potential application in antimicrobial polyurethane coating

Coumarin, thiazole and their respective derivative products are some of the oldest and most commonly known class of nitrogen and sulphur containing compounds. In recent years there has been considerable interest in this coumarin–thiazole derivatives, which have been reported to exhibit significant biological activity and are widely used as pharmaceuticals. They are capable of imparting anti-microbial activity properties when incorporated into polymers and polymer composites. In this research, coumarin–thiazole derivative 2-(2-amino-1,3-thiazol-4-yl)-3H benzo[f]chromen-3-one (compound III), was prepared and its structure was confirmed by means of its spectra data. It was also screened for its anti-microbial activity against eight different micro-organisms when physically incorporated into a polyurethane varnish formula. Experimental coatings were manufactured on a laboratory scale and applied by means of a brush on both glass and steel panels. The results of the biological activity indicated that the polyurethane varnishes containing the 2-(2-amino-1,3-thiazol-4-yl)-3H-benzo[f]chromen-3-one (compound III) derivative, exhibit a very good antimicrobial effect. The molecular modeling study revealed that it is biologically safe, it is active and it fulfills Lipinski's rule of five. The physical and mechanical resistances of the polyurethane varnish formulations were also studied to evaluate any drawbacks associated with the addition of the derivative. The studies indicate that the physical incorporation of compound III actually enhances slightly both the physical and mechanical properties.     

Pharmacological Evaluation and Preparation of Nonsteroidal Anti-Inflammatory Drugs Containing an N-Acyl Hydrazone Subunit

A series of anti-inflammatory derivatives containing an N-acyl hydrazone subunit (4a–e) were synthesized and characterized. Docking studies were performed that suggest that compounds 4a–e bind to cyclooxygenase (COX)-1 and COX-2 isoforms, but with higher affinity for COX-2. The compounds display similar anti-inflammatory activities in vivo, although compound 4c is the most effective compound for inhibiting rat paw edema, with a reduction in the extent of inflammation of 35.9% and 52.8% at 2 and 4 h, respectively. The anti-inflammatory activity of N-acyl hydrazone derivatives was inferior to their respective parent drugs, except for compound 4c after 5 h. Ulcerogenic studies revealed that compounds 4a–e are less gastrotoxic than the respective parent drug. Compounds 4b–e demonstrated mucosal damage comparable to celecoxib. The in vivo analgesic activities of the compounds are higher than the respective parent drug for compounds 4a–b and 4d–e. Compound 4a was more active than dipyrone in reducing acetic-acid-induced abdominal constrictions. Our results indicate that compounds 4a–e are anti-inflammatory and analgesic compounds with reduced gastrotoxicity compared to their respective parent non-steroidal anti-inflammatory drugs.     

Synthesis, characterization and photoconductive properties of optically active methacrylic polymers bearing side-chain 9-phenylcarbazole moieties

The synthesis of two novel optically active monomers containing 9-phenylcarbazole moieties, such as (S)-(+)-2-methacryloyloxy-N-[4-(9-carbazolyl)phenyl]succinimide [(S)-(+)-MCPS] and (S)-(+)-3-methacryloyloxy-N-[4-(9-carbazolyl)phenyl]pyrrolidine [(S)-(+)-MCPP], is described. Each monomer has been radically homopolymerized to afford the corresponding optically active polymeric derivatives, which have been fully characterized. Their spectroscopic, thermal and photoconductive properties were compared to those of the new achiral homopolymer poly[N-(2-methacryloyloxyethyl)-N-[4-(9-carbazolyl)phenyl]ethylamine] {poly[MCPE]}, devised as an optically inactive macromolecular model compound, as well as to analogue polymeric derivatives containing side-chain optically active carbazolyl moieties. The chiroptical properties of the chiral polymers are quantitatively higher than in the corresponding monomers. Owing to the substantially stereoirregular structure of the main chain, this suggests that the overall optical activity is mainly due to conformational dissymmetry of the macromolecules. Spectroscopic evidence suggests the presence in all polymeric derivatives of dipole-dipole interactions between the 9-phenylcarbazolyl chromophores, occurring as a consequence of their anchorage to the polymer backbone, which favours their aggregation and justifies their high decomposition temperatures.     

Mononuclear versus dinuclear palladacycles derived from 1,3-bis(N,N-dimethylaminomethyl)benzene: Structures and catalytic activity

Mononuclear and dinuclear palladacycles derived from 1,3-bis(N,N-dimethylaminomethyl)benzenes, [{Pd(Cl)}2,6-(Me₂NCH₂)₂C₆H₃] (1) and [1-{Pd(H₂O)(Py)}-5-{Pd(OTf)(Py)-2,4-(Me₂NCH₂)₂C₆H₂]-(OTf) (2), were synthesized and their structures were fully characterized. Complex 1 is a pincer complex with η³-mer NCN phenyl backbone, complex 2 is a bispalladium(II) complex with 1,2- and 4,5- two C,N-ortho phenyl backbone. Whereas the pincer complex 1 acted as a poor catalyst on methanolysis of fenitrothion, complex 2 demonstrated high catalytic activity in the same reactions, but there is no synergetic effect between two palladium ions. The results clearly indicate that a dissociable co-ligand in the palladacycle compounds significantly promotes the catalytic methanolysis.     

Thiazoles as corrosion inhibitors for mild steel in formic and acetic acid solutions

2-(N,N-dimethylamino) benzylidene imino-4-(4-methyl phenyl)-1,3-thiazole (DIMPT), 2-benzylidene imino-4-(4-methyl phenyl)-1,3-thiazole (BIMPT), 2-salicylidene imino-4-(4-methyl phenyl)-1,3-thiazole (SIMPT) and 2-cinnamylidene imino-4-(4-methyl phenyl)-1,3-thiazole (CIMPT) were synthesized in the laboratory and their influence on the inhibition of corrosion of mild steel in 20 formic acid and 20 acetic acid was investigated by weight loss and potentiodynamic polarization techniques. The inhibition efficiency of these compounds was found to vary with their nature and concentration, temperature, immersion time and acid concentration. The values of activation energy and free energy of adsorption of the thiazoles were calculated to investigate the mechanism of corrosion inhibition. The adsorption of all the thiazoles on mild steel surface was found to obey Langmuir adsorption isotherm. The potentiodynamic polarization result revealed that the compounds studied are mixed type inhibitors. Electrochemical impedance spectroscopy was used to investigate the mechanism of corrosion inhibition.     

Nitriles in heterocyclic synthesis: A new approach for the Synthesis of Thiazole derivatives

The reaction of 4-bromo-3-oxo-butyranilide ( 1 ) with KSCN afforded the thiocyanato derivative 2 . 2-Dicyanomethylthiazol-4-yl-acetanilide ( 3 ) was synthesised by reaction of 2 with malononitrile. A variety of substituted thiazol-2-yl malononitriles were prepared by reaction of 3 with hydroxylamine hydrochloride, phenylhydrazine and cinnamonitrile derivatives. The structure assignments of the new compounds are based mainly on ¹³C and ¹H-n.m.r. spectroscopic data.     

Synthesis and Biological Application of Isosteviol-Based 1,3-Aminoalcohols

Starting from isosteviol, a series of diterpenoid 1,3-aminoalcohol derivatives were stereoselectively synthesised. The acid-catalysed hydrolysis and rearrangement of natural stevioside gave isosteviol, which was transformed to the key intermediate methyl ester. In the next step, Mannich condensation of diterpenoid ketone, paraformaldehyde, and secondary amines resulted in the formation of 1,3-aminoketones with different stereoselectivities. During the Mannich condensation with dibenzylamine, an interesting N-benzyl → N-methyl substituent exchange was observed. Reduction of 1,3-aminoketones produced diastereoisomeric 1,3-aminoalcohols. Alternatively, aminoalcohols were obtained via stereoselective hydroxy-formylation, followed by oxime preparation, reduction, and finally, reductive alkylation of the obtained primary aminoalcohols. An alternative 1,3-aminoalcohol library was prepared by reductive amination of the intermediate 3-hydroxyaldehyde obtained from isosteviol in two-step synthesis. Cytotoxic activity of compounds against human tumour cell lines (A2780, SiHa, HeLa, MCF-7 and MDA-MB-231) was investigated. In our preliminary study, the 1,3-aminoalcohol function and N-benzyl substitution seemed to be essential for the reliable antiproliferative activity. To extend their application, a diterpenoid condensed with 2-phenylimino-1,3-thiazine and -1,3-oxazine was also attempted to prepare, but only formation of thioether intermediate was observed.     

Structure activity relationships of imidoN-alkyl semicarbazones,thiosemicarbazones and acethydrazones as hypolipidemic agents in rodents

A series of nitrogen substitutedN-butan-3-one derivatives of cyclic imides (phthalimide, substituted phthalimide,o-benzosulfimide, 1,8-naphthalimide, 2,3-dihydrophthalazine-1,4-dione and diphenimide) and their semicarbazone, thiosemicarbazone and acethydrazone derivatives were investigated for hypolipidemic activity in rodents. These compounds were generally potent hypolipidemic agents, lowering serum cholesterol levels on an average of 37% and serum triglyceride levels on an average of 29% after 16 days dosing at 20 mg/kg day intraperitoneally (I.P.) in mice. Several analogs, most notably the semicarbazone and acethydrazone derivatives of 1-N-(1,8-naphthalimido)-butan-3-one, demonstrated improved hypocholesterolemic activity relative to their ketone percursors. Similarly, the acethydrazone derivatives generally resulted in improved hypotriglyceridemic activity in each series of 2-(3-oxobutyl)-2,3-dihydrophthalazone-1,4-dione analogs tested. The thiosemicarbazones in mice generally resulted in a loss in hypolipidemic activity. Select compounds, 1-N-3-methylphthalimido butan-3-semicarbazone (Ig) and 1-(4-methoxyphthalazine-1(2H)-one)yl butan-3(N-acetyl)hydrazone (IVg), at 10 mg/kg/day orally administered to rats demonstrated potent hypolipidemic activity after 14 days. These compounds lowered liver, small intestine mucosa and aorta wall tissue lipids, e.g. cholesterol and triglycerides, and raised fecal excretion of cholesterol moderately and of triglyceride significantly. Rat serum lipoprotein fractions after treatment for 14 days showed that the two agents lowered VLDL cholesterol and raised HDL cholesterol content.     

Synthesis and characterization of macroporous silica modified with optically active poly[N‐(oxazolinylphenyl)acrylamide] derivatives for potential application as chiral stationary phases

Enantiopure acrylamide derivatives, (S)‐N‐[o‐(4‐methyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl]acrylamide and (R)‐N‐[o‐(4‐phenyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl]acrylamide, were synthesized through the acylation of chiral 2‐oxazolinylanilines. The radical polymerization of the chiral monomers was carried out with (3‐mercaptopropyl)trimethoxysilane as a chain‐transfer agent to obtain the corresponding optically active prepolymers with a trimethoxysilyl group. By immobilizing the prepolymers on porous silica gel via the grafting‐to method, we prepared a new chiral stationary phase (CSP) and characterized it by elemental analysis, thermogravimetry, and Fourier transform infrared spectroscopy. The enantioseparation capacities of the CSPs were evaluated with high‐performance liquid chromatography toward several racemic compounds, including 1,1′‐bi‐2‐naphthol, benzoin, 2‐amino‐1‐butanol, and loxoprofen sodium under the normal‐phase mode. The results indicate that the CSPs exhibited improved chromatographic performances compared to their brush‐type analogs obtained by the alternative grafting‐from approach. Also, the column packed with poly{(R)‐N‐[o‐(4‐phenyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl]acrylamide}‐bonded silica was found to have an extent of enantioselectivity in the chiral resolution of some unmodified amino acids with reversed‐phase eluents. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation of a Near-Infrared Ray Absorption Film from N-Phenylthiocarbamoyl Chitosan Derivative

We recently observed that the decanoylation of N-phenylthiocarbamoyl chitosan (2) with a mixture of decanoic anhydride and pyridine at 60 °C for 24 h afforded N,N-(decanoyl)phenythiocarbamoyl-/2-isothiocynato chitosan decanoate (3b) rather than the expected product N,N-(decanoyl)phenylthiocarbamoyl chitosan decanoate (3a). This result suggested that some of the N,N-(decanoyl)phenylthiocarmbamoyl groups had been converted to isothiocyanate groups during the decanoylation process. The subsequent reaction of compound 3b with aniline gave N,N-(decanoyl)phenylthiocarbamoyl/N-phenylthiocarbamoyl chitosan decanoate (4) in high yield. A solution of compound 4 in CHCl₃ was then added to a solution of copper decanoate (5) in the same solvent, and the resulting mixture was cast onto a glass plate to give a cast film. The film was annealed at 200 °C in an oven to give a greenish film, which showed good near-infrared absorption characteristic in the range of 800–2200 nm.     

Preparation and characterization of novel grafted polyethylene based azo-polymers bearing oligo(ethylene glycol) spacers

Novel grafted azo-polymers were prepared from commercial low density polyethylene plates (PE). First, precursor polymers were synthesized by reacting PE in the presence of acryloyl chloride using gamma radiation. Further esterification of the resulting grafted polymers with four new amino-nitro substituted azobenzene derivatives bearing oligo(ethylene glycol) segments: N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(5-hydroxy-3-oxapentas-1-yl)amine (RED-PEG-2), N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(8-hydroxy-3,6-dioxaoctas-1-yl)amine (RED-PEG-3), N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(11-hydroxy-3,6,9-trioxaundecas-1-yl)amine (RED-PEG-4) and N-methyl-N-{4-[(E)-(4-nitrophenyl)diazenyl]phenyl}-N-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecas-1-yl)amine (RED-PEG-6) led to the formation of branched azo-polymers. These polymers were characterized and their thermal and optical properties were studied. Besides, the influence of the irradiation dose, irradiation time and the structure of the dyes on the properties of the obtained polymers are discussed.     

Synthesis and Anticancer Evaluation of 1,4-Naphthoquinone Derivatives Containing a Phenylaminosulfanyl Moiety

1,4-Naphthoquinones are exceptional building blocks in organic synthesis and have been used to synthesize several well-known pharmaceutically active agents. Herein we report the synthesis, structural characterization, and biological evaluation of new phenylaminosulfanyl-1,4-naphthoquinone derivatives. We evaluated the cytotoxic activity of the synthesized compounds against three human cancer cell lines: A549, HeLa, and MCF-7. Most of the synthesized compounds displayed potent cytotoxic activity. Specifically, compounds 5 e [3,5-dichloro-N-(4-((4-((1,4-dioxo-3-(phenylthio)-1,4-dihydronaphthalen-2-yl)amino)phenyl)sulfonyl)phenyl)benzamide], 5 f [N-(4-((4-((1,4-dioxo-3-(phenylthio)-1,4-dihydronaphthalen-2-yl)amino)phenyl)sulfonyl)phenyl)-3,5-dinitrobenzamide], and 5 p [N-(4-((4-((1,4-dioxo-3-(phenylthio)-1,4-dihydronaphthalen-2-yl)amino)phenyl)sulfonyl)phenyl)thiophene-2-carboxamide] showed remarkable cytotoxic activity. The synthesized compounds showed low toxicity in normal human kidney HEK293 cells. The cytotoxic mechanism of compounds 5 e , 5 f , and 5 p was explored in MCF-7 cells. The results confirmed that these three compounds induce apoptosis and arrest the cell cycle at the G₁ phase. In addition, compounds 5 e , 5 f , and 5 p were found to induce apoptosis via upregulation of caspase-3 and caspase-7 proteins as well as by upregulation of the gene expression levels of caspases-3 and -7. Our findings demonstrate that compounds 5 e , 5 f , and 5 p could be potent agents against a number of cancer types.