Synthesis and Antimicrobial Activities of Novel Series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one Derivatives

In the present investigation, a novel series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one derivatives were synthesized by condensation of 2‐substituted‐4‐methylthiazole‐5‐carbaldehyde with 4‐(2‐substituted thiazol‐4‐yl)benzenamine followed by cyclo‐condensation with thioglycolic acid in toluene. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and Mass) methods. The title compounds were screened for quantitative antibacterial activity (minimal inhibitory concentration). All compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h and 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h show moderate to good antimicrobial activity, whereas compounds ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h ) also show moderate antifungal activity.     

Functionalization of Quinazolin‐4‐ones Part 3: Synthesis,Structures Elucidation,DNA‐PK,PI3K,and Cytotoxicity of Novel 8‐Aryl‐2‐morpholino‐quinazolin‐4‐ones

A series of novel 8‐aryl‐2‐morpholino quinazolines ( 11a – n , 12a – d , 14a – f , and 15 ) were synthesized from the precursor 2‐thioxo quinazolin‐4‐ones 8 . The 8‐aryl‐2‐morpholino quinazolines compounds were assayed for DNA‐PK and PI3K. All compounds showed low DNA‐PK % inhibition activity at 10 μM compound concertation, and the most active was 8‐(dibenzo[b,d]thiophen‐4‐yl) 12d with 38% inhibition. Similar pattern of PI3K α, β, γ, and δ isoforms inhibition activity at 10 μM were observed. The most active isoform was PI3K δ of 41% inhibition for 8‐(dibenzo[b,d]furan‐4‐yl) compound 11 . Most compounds were less active than expected in spite of the strong structural resemblance to known inhibitors ( NU7441 , 3 , 4 , and 6 ). Loss of activity could be attributed to the tautomerization to the aromatic enol (4‐OH), which could specify that the important functional group for the activity is the 4‐carbonyl (C=O) group. Alternatively, the aromatization of the pyrimidine heterocyclic ring could alter the conformation, and thus binding site, of the 2‐morpholine ring, which could reduce the compound‐receptor hydrogen bonding to the morpholine 4‐oxygen. Selected compounds displayed appreciable cytotoxicity with 6‐chloro‐8‐(dibenzo[b,d]thiophen‐4‐yl)‐2‐morpholinoquinazolin‐4(1H)‐one 11j exhibiting the greatest activity with an IC₅₀ of 9.95 μM. Therefore, the mechanism of the cytotoxicity of compound 11j were not through DNA‐PK or PI3K inhibition activity.     

Palladium Catalyzed Tricyclohexylphosphine Ligand Associated Synthesis of N‐(2‐(pyridine‐4‐yl)‐1H‐pyrrolo[3,2‐c]‐pyridin‐6‐yl‐(substituted)‐sulfonamide Derivatives as Antiproliferative Agents

A series of novel N‐(2‐(pyridine‐4‐yl)‐1H‐pyrrolo[3,2‐c]‐pyridin‐6‐yl‐(substituted)‐sulfonamide derivatives were synthesized from 2‐bromo‐6‐nitro‐1H‐pyrrolo[3,2‐c]pyridine through a series of reactions including Suzuki reaction, reduction, protection, and sulfonamide coupling. All the synthesized compounds were screened for anticancer activity against MCF‐7, HeLa, A‐549, and Du‐145 cancer cell lines by the MTT assay. The preliminary bioassay suggests that most of the compounds show antiproliferation with different degrees. Doxorubicin was used as a positive control. Among the synthesized compounds, 8d and 8h were most active compared with the standard in cell line data. The synthesized compounds 8d and 8h show IC₅₀ values in the range of 1.88–5.16 μM for all the cell lines. Compounds 8d and 8h were further studied for a panel of eight human kinase at 10 μM concentrations and the result shows 64% to 70% inhibitions for both Aurora‐A and Aurora‐B kinase.     

Design,Synthesis, and Evaluation of 3‐((4‐(t‐Butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones as Neuraminidase Inhibitors

A series of novel 3‐((4‐(t‐butyl)‐2‐(2‐benzylidenehydrazinyl)thiazol‐5‐yl)methyl)quinolin‐2(1H)‐ones ( 7a – 7z ) were designed, synthesized and evaluated for their ability of inhibiting neuraminidase (NA) of in?uenza H1N1 virus. Some compounds displayed moderate influenza NA inhibitory activity. Compound 7l with the scaffold of 2‐(2‐(2‐methoxybenzylidene)hydrazinyl)thiazole was the best one, exhibiting moderate NA inhibitory activity with IC₅₀ of 44.66 µmol/L. Structure‐activity relationship showed that compounds with methoxy or hydroxy groups at the ortho position, fluorine and nitro groups at the meta position and chlorine and bromine groups at the para position of phenyl ring were more active. Docking study indicated that compound 7l has important interactions with some key residues (including Asp151, Glu119, Arg292, Tyr406, and Asn347) and binds to 430‐cavity adjacent to NA active site.     

Design and Synthesis of 3‐Substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones as a New Class of Anticonvulsants

A new series of 3‐substituted‐thiazolyl‐2‐iminothiazolidin‐4‐ones were synthesized by nucleophilic substitution of p‐substituted‐thiazol‐2‐yl‐chloroacetamides with potassium thiocyanide by cyclization. The starting material p‐substituted‐thiazol‐2‐yl‐chloroacetamides were synthesized from p‐substituted‐thiazol‐2‐yl‐amines with chloroacetyl chloride, which in turn was prepared from one pot reaction of substituted aryl acetophenone and amino group of thiourea. The title compounds were investigated for their anticonvulsant activity. Among the tested compounds, compound 3‐(4‐(4‐fluorophenyl)thiazol‐2‐yl)‐2‐iminothiazolidin‐4‐one ( 16 ) emerged as the most active compound of the series, and it is moderately more potent than the reference standard diazepam.     

Synthesis and Antimicrobial Activity of Novel 2‐Substituted Phenoxy‐N‐(4‐substituted Phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl)acetamide Derivatives

A series of 2‐substituted phenoxy‐N‐(4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazole‐2‐yl)acetamide derivatives 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r , 8s , 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine 5 . Their structures were confirmed by ¹H NMR, ¹³C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae , Phytophthora infestans , and Paralepetopsis sasakii ) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo ) and Xanthomonas axonopodis pv. citri (Xac )] showing promising results. In particular, 8b , 8f , 8g , and 8h exhibited excellent antibacterial activity against Xoo , with 50% effective concentration (EC₅₀) values of 35.2, 80.1, 62.5, and 82.1 µg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 µg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.     

Synthesis and In vitro Antitumor Screening of Novel 2,7‐Naphthyridine‐3‐carboxylic Acid Derivatives

New derivatives of 2,7‐naphthyridine‐3‐carboxylic acid were synthesized. We report the hydrolysis, chlorination, alkylation, and amination of the 2,7‐naphthyridine esters 1 , 2 . A series of Schiff's bases 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 9a , 9b , 9b' , 9c , 9d , 9e were produced by treating the obtained hydrazides 6 and 7 with aromatic aldehydes. The anticancer activities of the obtained derivatives were examined. Eighteen of the 24 newly synthesized compounds were qualified by the National Cancer Institute NCI (Bethesda, MD, USA) for in vitro screening against 60 different human tumor cell lines. The most active compound 8i was evaluated against a 60‐cell panel at five concentration levels and proved to be most sensitive towards central nervous system cancer (SF‐539), with GI₅₀ = 0.70 µmol, total growth inhibition = 5.41 µmol, and LC₅₀ = 53.7 µmol.     

Synthesis and Anticancer Evaluation of Some Novel Thiophene,Thieno[3,2‐d]pyrimidine,Thieno[3,2‐b]pyridine,and Thieno[3,2‐e][1,4]oxazepine Derivatives Containing Benzothiazole Moiety

In an attempt to establish novel candidate with promising anticancer activity, two derivatives of (benzo[d]thiazol‐2‐yl)thiophene backbone 1 and 14 were synthesized, and they further reacted with various chemical reagents to afford the corresponding substituted thiophene derivatives 6 , 8 , 10 , 15 , 17 , and 20 , thieno[3,2‐d]pyrimidine derivatives 2 – 5 , 7 , 9 , 16 , 21 , 23 , and 24 , thieno[3,2‐b]pyridine derivatives 11 – 13 , and thieno[3,2‐e][1,4]oxazepine derivative 18 . Structures of prepared compounds were affirmed via spectral and elemental data. Among the obtained compounds, seven derivatives 2 , 3 , 4 , 5 , 11 , 12 , and 13 were chosen by National Cancer Institute, USA. Such compounds were screened for their antitumor activity versus 60 cancer cell lines in one‐dose (10 μmol) screening assay. The outcomes showed that all selected compounds exhibited moderate to high anticancer activity towards many cancer cell lines among which compounds 5 and 11 exerted potent antitumor activity against numerous malignant growth cell lines particularly Ovarian Cancer IGROV1.     

Synthesis of 5‐chloro‐2‐methyl‐3‐(5‐methylthiazol‐2‐yl)‐4(3H)‐quinazolinone and related compounds with potential biological activity

Eight new 2‐methyl‐4(3H)‐quinazolinones (8a‐8d, 9c, 9d, 10c, 10d) with one or two chlorine atoms in the benzene ring and a 5‐methyl‐1,3‐thiazol‐2‐yl, 4‐methyl‐1,3‐thiazol‐2‐yl, and 5‐ethyl‐1,3,4‐thiadiazol‐2‐yl substituent in position 3 of the heterocyclic ring were synthesized and characterized. The two step procedure (Scheme 1) utilizes chlorosubstituted anthranilic acids (3a‐3d) and acetic anhydride as the starting materials, with the respective chlorosubstituted 2‐methyl‐4H‐3,1‐benzoxazin‐4‐ones (4a‐4d) as the intermediates. The quinazoline derivatives were characterized by their melting points, elemental analyses and the mass, ultraviolet, infrared, and ¹H and ¹³C nmr spectra. The new compounds are expected to be biologically active.     

Facile Synthesis of Novel 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one Derivatives as Potential Anticancer Agents

A series of 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 6a – l ) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross‐coupling reactions were successfully applied to the preparation of title compounds in good‐to‐high yields. In the synthetic sequences, 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehydes ( 2 ) were found to react with ammonium thiocyanate to yield the corresponding 3‐(isothiazol‐5‐yl)‐2H‐chromen‐2‐ones ( 3 ). These derivatives were brominated with N‐bromo succinamide to yield the corresponding regioselective 3‐(4‐bromoisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 4 ). Finally, compound 4 was treated with various phenyl/pyrazole/7H –pyrrolo[2,3‐d]pyrimidinyl boronic acids 5a – l in the presence of K₂CO₃ and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a – l . All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b , 6g , 6h , and 6l displayed moderate cytotoxic activity against the tested cell lines.     

Novel 5‐Methyl‐2‐[(un)substituted phenyl]‐4‐{4,5‐dihydro‐ 3‐[(un)substituted phenyl]‐5‐(1,2,3,4‐tetrahydroisoquinoline‐2‐yl)pyrazol‐1‐yl}‐oxazole Derivatives: Synthesis and Anticancer Activity

Eleven novel 5‐methyl‐2‐[(un)substituted phenyl]‐4‐{4,5‐dihydro‐3‐[(un)substituted phenyl]‐5‐(1,2,3,4‐tetrahydroisoquinoline‐2‐yl)pyrazol‐1‐yl}‐oxazole derivatives were synthesized and characterized by elemental analysis, ESI‐MS, ¹H NMR and ¹³C NMR. All of the compounds have been screened for their antiproliferative activities against PC‐3 cell (human prostate cancer) and A431 cell (human epidermoid carcinoma cancer) lines in vitro. The results revealed that compounds 4g , 4j and 4k exhibited the strong inhibitory activities against the PC‐3 cell lines (with IC₅₀ values of 2.8±0.11, 3.1±0.10 and 3.0±0.06 μg/mL, respectively).     

Synthesis and Antifungal Screening of 2‐(2‐Aryl‐4‐methyl‐thiazol‐5‐yl)‐5‐((2‐aryl/benzylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole Derivatives

A new series of synthesis and biological screening of 2‐(2‐aryl‐4‐methyl‐thiazol‐5‐yl)‐5‐((2‐aryl/benzylthiazol‐4‐yl)methyl)‐1,3,4‐oxadiazole derivatives 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i was achieved by condensation of 2‐(2‐aryl/benzylthiazol‐4‐yl)acetohydrazide 2a , 2b , 2c with 4‐methyl‐2‐arylthiazole‐5‐carbaldehyde 3a , 3b , 3c followed by oxidative cyclization of N'‐((4‐methyl‐2‐arylthiazol‐5‐yl)methylene)‐2‐(2‐aryl/benzylthiazol‐4‐yl)acetohydrazide 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i using iodobenzene diacetate as oxidizing agent. All the synthesized compounds were screened for their in vitro antifungal activity against Candida albicans, Candida tropicalis, Aspergillus niger, and Aspergillus flavus. Some of the synthesized compounds showed good antifungal activity.     

Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2‐[N‐(1H‐Tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazoles

In this study, we report the synthesis a series of novel 2‐[N‐(1H‐tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazole derivatives ( 7a – e ) which have potential opioid antagonist and agonist. The substitution reaction of 6,14‐endo‐ethenotetrahydrothebaine‐7α‐carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4a – e in good yields. The treatment of compounds 4a – e with POCl₃ caused the conversion of side‐chain of compounds 5a – e into 1,3,4‐oxadiazole ring at C(7) position; thus, compounds 5a – e were obtained. Subsequently, cyanamides ( 6a – e ) were prepared from compounds 5a – e and then compounds 7a – e were synthesized by the azidation of 6a – e with NaN₃. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C APT, 2D‐NMR (COSY, NOESY, HMQC, HMBC) and high‐resolution mass spectral data.     

Synthesis,structure and in vitro cytotoxicity testing of some 2‐aroylbenzofuran‐3‐ols

Five 2‐aroyl‐5‐bromobenzo[b]furan‐3‐ol compounds (two of which are new) and four new 2‐aroyl‐5‐iodobenzo[b]furan‐3‐ol compounds were synthesized starting from salicylic acid. The compounds were characterized by mass spectrometry and ¹H NMR and ¹³C NMR spectroscopy. Single‐crystal X‐ray diffraction studies of four compounds, namely, (5‐bromo‐3‐hydroxybenzofuran‐2‐yl)(4‐fluorophenyl)methanone, C₁₅H₈BrFO₃, (5‐bromo‐3‐hydroxybenzofuran‐2‐yl)(4‐chlorophenyl)methanone, C₁₅H₈BrClO₃, (5‐bromo‐3‐hydroxybenzofuran‐2‐yl)(4‐bromophenyl)methanone, C₁₅H₈Br₂O₃, and (4‐bromophenyl)(3‐hydroxy‐5‐iodobenzofuran‐2‐yl)methanone, C₁₅H₈BrIO₃, were also carried out. The compounds were tested for their in vitro cytotoxicity on the four human cancer cell lines KB, Hep‐G2, Lu‐1 and MCF7. Six compounds show good inhibiting abilities on Hep‐G2 cells, with IC₅₀ values of 1.39–8.03 µM.     

Synthesis of Biologically Active[4-(4-Bromophenyl)-2-thiazolyl]hydrazones and their D-Galactose Derivatives

Benzaldehyde [4‐(4‐bromophenyl)thiazol‐2‐yl]hydrazones 5a – 5d were prepared by reacting the thiosemicarbazones 2a – 2d with 2,4′‐dibromoacetophenone ( 1 ) in absolute ethanol. Acetylation of 5a and 5b with Ac₂O/Py at room temperature gave the N‐acetyl derivatives 6a and 6b . 4‐Methyl‐2‐pentanone/cyclopentanone [4‐(4‐bromo‐phenyl)thiazol‐2‐yl]hydrazones ( 8a ) and ( 8b ) were similarly obtained from the reaction of 1 with the thiosemicarbazones 7a and 7b , respectively. Cyclization of D‐galactose thiosemicarbazone ( 9 ) and its tautomers 10 and 11 with 1 afforded an equilibrium mixture of the acyclic 2‐thiazolylhydrazone 12 , together with its respective cyclic galactosyl derivatives 13 and 14 , whose structures were studied by using ¹H and ¹³C NMR spectra. The antimicrobial activity of the synthesized thiazole derivatives was evaluated in vitro by using an agar diffusion technique, and some of these compounds showed potential activity against Candida albicans.     

Synthesis,Reactions, Characterization and Biological Evaluation of 2,3′‐Bipyridine Derivatives (III)

1‐Pyridin‐3‐yl‐3‐(2‐thienyl of 2‐furyl)prop‐2‐en‐1‐ones 1a , 1b reacted with 2‐cyanoethanethioamide 2 to afford the corresponding 4‐(thiophen‐2‐yl or furan‐2‐yl)‐6‐sulfanyl‐2,3′‐bipyridine‐5‐carbonitriles 3a , 3b . The synthetic potentiality of compounds 3a , 3b were investigated in the present study via their reactions with several active halogen containing compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 5 , 5a , 5b . Our aim here is the synthesis of 4‐(2‐thienyl or 2‐furyl)‐6‐pyridin‐3‐ylthieno[2,3‐b]pyridin‐3‐amines 6a , 6b , 6c , 6d , 6e , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n ,via 6‐(alkyl‐thio)‐4‐(2‐thienyl or 2‐furyl)‐2,3′‐bipyridine‐5‐carbonitriles 5a , 5b , 5c , 5d , 5e , 5i , 5j , 5k , 5l , 5m . The structures of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, ¹H‐NMR, mass spectra, as well as that of elemental analyses. Anti‐cancer, anti‐Alzheimer, and anti‐COX‐2 activities were investigated for all the newly synthesized heterocyclic compounds.     

A Facial Synthesis and Anticancer Activity of (Z)‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted Acid

In order to explore the anticancer and antimicrobial activity associated with the thiazole framework, we synthesized the new series (Z )‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted acid derivatives 6a – l . All the synthesized compounds were evaluated for anticancer and antimicrobial activity in vitro. Among these, the compounds 6a , 6b, 6c , 6e , 6f , 6g , 6h , 6i , 6j , and 6k showed highest antibacterial and antifungal activity. The compound 6a exhibited significant antibacterial activity against Bacillus subtilis , whereas compound 6j displays significant antifungal activity against fungal strains, that is, A. oryzae . The in vitro anticancer studies revealed that 6e , 6g , 6h , 6k , and 6l are the most active compounds against MCF‐7 and BT‐474 human breast cancer cell lines, which can be regarded as the promising drug candidate for development of anticancer drugs.     

Synthesis and Antimicrobial Activity of Some Novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles and 1,3,4‐thiadiazoles

A series of novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles ( 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h ) and 1,3,4‐thiadiazoles ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i ) were synthesized from thiosemicarbazide ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j ). The structures of these newly synthesized compounds were confirmed on the basis of IR, ¹H‐NMR, mass spectral techniques, and elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The compounds 7d , 7j , 8a , 9a , 9b , and 9i exhibited promising antibacterial activity against the tested strains, whereas some compounds were found to be active against one of the tested bacterial strains.     

Et3N‐Prompted Efficient Synthesis of Anthracenyl Pyrazolines and Their Cytotoxicity Evaluation against Cancer Cell Lines

A series of anthracenyl pyrazoline derivatives ( 3a – o ) were synthesized with an aim to evaluate their in vitro anticancer activities. Anthracenyl pyrazoline compounds were prepared by the reaction between various anthracenyl chalcones ( 1a – o ) and hydrazine hydrate ( 2 ). The reactions were carried out under reflux in the presence of triethylamine and ethanol for 24 h, and the obtained yields were from good to excellent (90–97%). The structure of each compound is well characterized by IR, ¹H‐NMR, ¹³C‐NMR, elemental analyses, and mass spectroscopic technics, and the molecular structures of compounds 3d and 3e were solved by single‐crystal X‐ray crystallographic methods. The newly synthesized compounds ( 3a – o ) were evaluated for their in vitro cytotoxic studies against four human cancer cell lines MCF‐7 (breast cancer cell lines), SK‐N‐SH (neuroblastoma cancer cell lines), HeLa (cervical cancer cell lines), and HepG2 (liver cancer cell lines), and the screening results show strong cytotoxic effects for most of the synthesized compounds against the three cell lines except SK‐N‐SH cells. Notably, compounds 3a , 3j , 3l , 3m , 3n , and 3o showed a highly potential activity against HeLa cells (IC₅₀: 0.22, 0.3, 0.3, 0.10, 0.25, and 0.25 μM), while compounds 3i , 3k , 3l , and 3m showed a significant cytotoxic activity in HepG2 cells (IC₅₀: 0.22, 0.44, 0.40, and 0.22 μM), whereas compounds 3a , 3b , 3d , and 3e exhibit a promising cytotoxicity against MCF‐7 cells (IC₅₀: 0.73, 0.495, 0.493, and 0.66 μM).     

Synthesis and Evaluation of Pyrido[2,3‐d]pyrimidine and 1,8‐Naphthyridine Derivatives as Potential Antitumor Agents

New series of pyrido[2,3‐d]pyrimidine and 1,8‐naphthyridine derivatives were synthesized from 2‐amino‐6‐(phenoxathiin‐2‐yl)‐4‐(thiophene‐2‐yl) nicotinonitrile as starting material, and their structures were characterized on the basis of the spectral data. Most of the synthesized compounds were evaluated for their cytotoxic activity against two cancer cell lines, namely, breast cancer Michigan Cancer Foundation‐7 (MCF‐7) and prostate cancer human prostatic carcinoma cell line (PC‐3) using MTT assay. Some of these compounds showed potent cytotoxic effect concluded from their IC₅₀ values.