Cytotoxic Isoprenylated Flavonoids from the Roots of Sophora flavescens

Three new flavonoids, which are isoprenylated by fused 2,2‐dimethyl‐3,4‐dihydro‐2H‐pyran moieties, were isolated from the roots of Sophora flavescens and named flavenochromanes A–C ( 1 – 3 ). Their structures were elucidated by spectroscopic methods, including 2D‐NMR techniques. Flavenochromane C ( 3 ) showed strong cytotoxic activity against A549 (lung carcinoma), 1A9 (ovarian carcinoma), KB (epidermoid carcinoma of the nasopharynx), and KB‐Vin (drug‐resistant variant KB) cell lines with IC₅₀ values ≤1.7 μM , and significant activity against the MCF‐7 (breast adenocarcinoma) cell line with an IC₅₀ value of 3.6 μM . Flavenochromane B ( 2 ) displayed slightly lower inhibitory effects (IC₅₀ 3.2–6.9 μM ) as compared with 3 .     

Medicinal Flowers. Part 29. Acylated Oleanane‐Type Triterpene Bisdesmosides: Perennisaponins G,H, I,J, K,L, and M with Pancreatic Lipase Inhibitory Activity from the Flowers of Bellis perennis

The MeOH extract from the flowers of Bellis perennis was found to show pancreatic‐lipase inhibitory activity (IC₅₀ 455 μg/ml). From the extract, seven new triterpene saponins named perennisaponins G ( 1 ; IC₅₀ 163 μM ), H ( 2 ; 137 μM ), I ( 3 ; 147 μM ), J ( 4 ; 148 μM ), K ( 5 ; 223 μM ), L ( 6 ; 81.4 μM ), and M ( 7 ; 195 μM ) were isolated as pancreatic lipase inhibitors. The stereostructures of 1 – 7 were elucidated on the basis of chemical and spectroscopic evidence.     

Two New Prenylated Xanthones from the Pericarp of Garcinia mangostana (Mangosteen)

Two new prenylated xanthones (=9H‐xanthen‐9‐ones), garcimangosxanthones D ( 1 ) and E ( 2 ), together with the six known xanthones 3 – 8 , were isolated from the pericarp of Garcinia mangostana. Their structures were determined by analysis of their spectroscopic data. All of the isolated compounds were biologically evaluated for their in vitro cytotoxic activity against A549, Hep‐G2, and MCF‐7 human‐cancer cell lines and antioxidant activity. Compound 1 exhibited moderate cytotoxicity against Hep‐G2 (IC₅₀=19.2 μM ) and weak cytotoxicity against MCF‐7 (IC₅₀=62.8 μM ) cell lines, and compound 2 showed moderate cytotoxicity against A549, Hep‐G2, and MCF‐7 cell lines with IC₅₀ values of 12.5–20.0 μM (Table 2). Both compounds 1 and 2 demonstrated a weak antioxidant activity with ferric reducing antioxidant power (FRAP) values of 41±7 and 130±4 μmol/g, respectively (Table 3).     

Chemical Constituents from Alafia Barteri Oliv. Leaves with Cytotoxic Activity

Methanol extract of Alafia barteri leaves showed cytotoxic activity on leukaemia carcinoma K562, and hepatic liver cancer cells WRL (IC₅₀ values 193.1 and 225.0 μM respectively). Isolation of the extract gave ursane triterpenoid, 28‐acety‐urs‐5,20‐dien‐2β,3β,24α‐triol, 1 , together with undecanol, 2 , stigmasterol, 3 and octadecanoic acid, 4 . The structures of these compounds were identified by spectroscopic analysis, including MS, 1D and 2D NMR, and supported with literature data. Compound 1 exhibited cytotoxic activity against K‐562 at 50 and 100 μM concentrations with IC₅₀ 74.22 μM, while compounds 2 , 3 and 4 showed low inhibition of WRL, MCF‐7 and COLO cell lines.     

Topo I inhibition,DNA photocleavage,Molecular docking and cytotoxicities of two new phenanthroline-based ruthenium complexes

Two ruthenium complexes containing a new phenanthroline-based ligand pai (pai = 2-(5-(1, 10- phenanthroline))-1H-acenaphtho[1′,2′:4,5]imidazole) were synthesized and characterized. Two ruthenium complexes were found to cleave DNA under irradiation, interact with CT-DNA by intercalation. Furthermore, DNA topoisomerase inhibition experiments indicated that complex 2 exhibited higher topoisomerase I inhibition activity (IC₅₀ = 10 μM) than complex 1 (IC₅₀ = 40 μM). Molecular modeling studies revealed that complex 2 stabilized Top1cc complex via π-π interaction and the formation of hydrogen bond. The cytotoxicity of complexes 1 and 2 against Eca-109 and A549 cells was also evaluate by MTT method, indicating that complex 2 exhibited good anticancer activity against Eca-109 cells (IC₅₀ = 17.23 ± 0.22 μM), but two ruthenium complexes displayed weak anticancer activity against A549 cells.     

Synthesis of Novel Triazole Incorporated Thiazolone Motifs Having Promising Antityrosinase Activity through Green Nanocatalyst CuI-Fe3O4@SiO2 (TMS-EDTA)

In the present work, novel 5-((1-benzyl-1,2,3-triazol-4-yl)methoxybenzylidene)-2-(arylamino)thiazol-4-one thiazolone incorporated triazole derivatives have been designed as tyrosinase inhibitors. The compounds were synthesized through click reaction in good yield. Moreover, the antityrosinas activity of the synthesized derivatives was evaluated. In the search for establishing a click copper-catalyzed azide/alkyne cycloaddition (CuAAC) reaction under strict conditions, in terms of a novel air-stable, a recyclable and efficient magnetic catalyst was planned for new triazole derivatives as a well-organized copper iodide supported on the functionalized Fe₃O₄@SiO₂ core-shell (CuI/Fe₃O₄@SiO₂(TMS-EDTA) nanoparticles). The engineered nanocatalyst synthesized for the first time and characterized by different methods, including FT-IR spectroscopy, XRD, FESEM, EDX, TEM, TGA, and BET analysis. The excellent catalytic performance in ethanol with high surface area (351.7 m²g⁻¹) and short reaction time for diverse functional groups (120–200 min), no use of toxic solvents, reusability of the catalyst, and using eco-friendly conditions are the advantageous of this work. Moreover,the nanocatalyst can be used at least five times without any significant decrease in the yield of the reaction. The thiazolidine-triazole derivatives 9a , 9c , 9e , and 9 g showed promising tyrosinase inhibitory activity with IC₅₀ values in the range of 5.90–9.81 μM. The compounds were found to be considerably more potent tyrosinase inhibitors than the reference inhibitor kojic acid (IC₅₀ = 18.36 μM).     

Novel Ferrocenyl Linked Pyrazoline Analogs as Potent Antiamoebic Agents

Some novel ferrocenyl linked pyrazoline analogs were synthesized, well characterized, and evaluated for in vitro antiamoebic activity against HM1 : IMSS strain of Entamoeba histolytica. Most of the compounds exhibited higher antiamoebic activity with the IC₅₀ value in the range of 0.12–1.20 μM, than the reference drug metronidazole, (IC₅₀ value of 1.78 μM). Compound 9 showed the most promising antiamoebic activity (IC₅₀ = 0.12 μM), concluding that these compounds hold immense potential to be employed as new antiamoebic agents. Also, being novel, they can be a solution to the increasing resistance that has posed a major problem globally.     

Microwave-assisted synthesis and biological evaluation of new thiazolylhydrazone derivatives as tyrosinase inhibitors and antioxidants

In this work, we have synthesized a series of 2-thiazolylhydrazone derivatives ( 1–27 ) and investigated their biological activities as tyrosinase inhibitors and antioxidants. Some compounds showed potent tyrosinase inhibitory activities and 4-(2-(2-(1-(4-Aminophenyl)ethylidene)-hydrazinyl)thiazol-4-yl) phenol ( 26 ) showed more potent inhibitory effect than the standard tyrosinase inhibitor kojic acid (IC₅₀: 9.8 μM vs. 23.6 μM). Compounds 2 , 14 , and 26 exhibited high antioxidant activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The structure–activity relationship (SAR) indicated that the substitutions of bromine, hydroxyl group, and amino groups cause great effect to the inhibition effect against tyrosinase. The mechanism and kinetic studies demonstrated that the inhibitory effect of compound 26 on the tyrosinase by acting as the reversible and uncompetitive inhibitor. Docking studies suggests that compound 26 interacts strongly with mushroom tyrosinase via hydrogen bonding.     

Bisubstrate Inhibitors for the Enzyme Catechol O‐Methyltransferase (COMT): Dramatic Effects of Ribose Modifications on Binding Affinity and Binding Mode

Inhibition of the enzyme catechol O‐methyltransferase (COMT) is of significant interest in the therapy of Parkinson's disease. Described herein are structural analogs of the potent bisubstrate inhibitor (?)‐ 1 (IC₅₀=9 nM ; Table 1) for COMT, with target modifications of the central ribose moiety. Their synthesis involves, as key intermediates, adenosine derivatives, which are transformed to the potential bisubstrate inhibitors by a similar sequence of six steps (Schemes 1–4). The compounds were submitted to an enzymatic assay for determination of their in vitro inhibitory activity against COMT, and the inhibition mechanism with respect to the binding side of the cofactor S‐adenosylmethionine (SAM) was analyzed by kinetics measurements (Fig. 3). Both binding affinity and binding mode were exceedingly sensitive towards modifications of the ribose moiety (Table 1). Removal of the 2′‐OH group upon changing from (?)‐ 1 to (?)‐ 2 (IC₅₀=28 μM ) led to a reduction in binding affinity by more than three orders of magnitude. At the same time, competitive inhibition kinetics with respect to the SAM binding site was maintained, thereby supporting a bisubstrate binding mode. Unlike (?)‐ 2 , the dideoxyribose inhibitor (?)‐ 3 (IC₅₀=3 μM ) showed a mixed and the cyclopentane derivative (+)‐ 4 (IC₅₀=1 μM ) an uncompetitive inhibition mechanism with respect to the SAM binding site. In the complex of the latter, the adenine‐substituted cyclopentane ring orients most probably towards the surface of the enzyme into the surrounding solution. The enantiomeric compounds (?)‐ 5 (IC₅₀=43 μM ) and (+)‐ 5 (IC₅₀=141 μM ), wherein the ribose had been replaced by a pyrrolidine ring, showed only low binding affinity.     

Antiprotozoal Activity and Cytotoxicity of Novel 1,7‐Dioxadispiro[5.1.5.2]pentadeca‐9,12‐dien‐11‐one Derivatives from Amomum aculeatum

Cytotoxicity against the KB cancer cell line as a lead bioactivity‐guided fractionation of the petroleum ether extract of rhizomes of Amomum aculeatum Roxb. led to the isolation of three novel dioxadispiro[5.1.5.2]pentadeca‐9,12‐dien‐11‐one derivatives. The structures of aculeatin A ( 1 ), aculeatin B ( 2 ), and aculeatin C ( 3 ) were established as rel‐(2R,4R,6S)‐ and rel‐(2R,4R,6R)‐4‐hydroxy‐2‐tridecyl‐1,7‐dioxadispiro[5.1.5.2]pentadeca‐9,12‐dien‐11‐one ( 1 and 2 , resp.) and rel‐(2R,4R,6R)‐2‐[4‐(3‐dodecyl‐2‐heptyl‐3‐hydroxy‐6‐oxocylohexa‐1,4‐dienyl)‐2‐oxobutyl]‐4‐hydroxy‐1,7‐dioxadispiro[5.1.5.2]pentadeca‐9,12‐dien‐11‐one ( 3 ) by extensive spectroscopic analyses, particularly ¹³C‐NMR, inverse‐gated ¹³C, HMQC, HMBC, NOESY, and INADEQUATE NMR experiments as well as mass spectrometry. The aculeatins represent a novel type of natural products. All compounds showed high cytotoxicity against the KB cell line: 1 , IC₅₀=1.7 μM ; 2 , IC₅₀=2.0 μM ; 3 , IC₅₀=1.6 μM . Additional testing against two Plasmodium falciparum strains as well as against trypomastigote forms of Trypanosoma brucei rhodesiense and Trypanosoma cruzi showed strong activities, particularly against P. falciparum strain K1 ( 1 , IC₅₀=0.18 μM ; 2 , IC₅₀=0.43 μM ; 3 , IC₅₀=0.37 μM ).     

Design,synthesis, anticancer activity,and in silico studies of novel imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives

A novel series of imidazo[1,2-a]pyridine based 1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their anticancer activity against two different human cancer cell lines. Most of the synthesized compounds displayed anticancer activity with IC₅₀ values from 2.35 to 120.46 μM. Furthermore, compounds 9b , 9c, 9d, 9f , and 9j showed potent inhibitory activity against cancer cell lines, with IC₅₀ values close to that of standard drug. It is important to note that compound 9d was more potent than the standard drug cisplatin with IC₅₀ values of 10.89 and 2.35 μM against Hela cell line and MCF-7 cell line, respectively.     

Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation

Abstract

Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC₅₀ 0.30 to 1.01 mg mL^?1. Compound 3 exhibited activity against HepG-2 cell lines with IC₅₀ 8.99?μM. Compound 7 exhibited activity against Hela cell lines with IC₅₀ 2.53?μM and BGC-823 cell lines with IC₅₀ 7.77?μM. Moreover, compound 7 showed antioxidant with IC₅₀ 12?µM compared to the positive control with IC₅₀ 77?µM. Compound 16 exhibited activity against HepG-2 cell lines with IC₅₀ 1.05?μM and MCF-7 cell lines with IC₅₀ 1.89?μM. These results indicated that this plant might be potential in natural medicine and healthy food.     

Protein Protection by Antioxidants: Development of a Convenient Assay and Structure‐Activity Relationships of Natural Polyphenols

In this work, a convenient test of antioxidant activity was developed, with BChE‐contaminated HSA as the target of AAPH‐induced oxidation and its esterase activity as the marker of protein integrity or degradation. The method is relatively simple, of low cost, and convenient to use. Its application to natural polyphenols showed that quercetin ( 1 ), verbascoside ( 2 ), chlorogenic acid ( 3 ), caffeic acid ( 4 ), 1,3,6,7‐tetrahydroxyxanthone ( 5 ), and mangiferin ( 6 ), are good antioxidants (IC₅₀<9 μM ). 1,5‐Dihydroxy‐3‐methoxyxanthone ( 7 ), flemichin D ( 8 ), and cordigone ( 9 ) showed modest activities (ca. 50 μM <IC₅₀<350 μM ), whereas danthrone ( 10 ) was inactive. Complementary experiments with two of the more active antioxidants, namely quercetin ( 1 ) and chlorogenic acid ( 3 ) showed that both antioxidants were better radical scavengers than chain‐breaking antioxidants. The relative adiabatic oxidation potential (ΔH_ox), the relative H‐bond dissociation energy (ΔH_abs), and the first oxidation potential measured by cyclic voltammetry were found to be related to the radical‐scavenging activity of these antioxidants.     

Synthesis of novel triazoloquinoxaline-pyrazole hybrids as antiproliferatives,EGFR inhibitors,and apoptosis inducers

Novel triazoloquinoxaline-pyrazole hybrids have been developed and synthesized. All derivatives' anticancer activity has been evaluated using Sulforhodamine-B (SRB) assay for cancer cell lines MCF-7, HepG-2, and HCT-116. Compound 12b was 2-fold more cytotoxic than Doxorubicin, while 12a , c demonstrated comparable cytotoxicity to the reference Doxorubicin. Further investigations on the most active derivatives 12a-c were done to study their inhibitory activity on two EGFR subtypes wild EGFR and mutant EGFR (L858R) tyrosine kinases in MCF-7 cell lines. Compound 12b exhibited potent inhibitory activity toward wild EGFR (IC₅₀: 0.98 μM) when compared to Gefitinib (IC₅₀:18.07 μM). 12b also possessed a marked inhibition against mutant EGFR (L858R-TK) exhibiting (IC₅₀:27.45 μM) in comparison to Lapatinib (IC₅₀: 61.06 μM). Compound 12b improved the active Caspase-3 value and the BAX/Bcl-2 reference. Furthermore, 12b showed G2/M cell cycle arrest induced apoptosis in cell line MCF-7. In addition, the most active derivatives have been orally bioavailable as shown in the in silico determination of the ADME characters. The binding pattern of compound 12b was also studied by molecular docking.     

Synthesis and anticancer activity of benzotriazole derivatives

A series of benzotriazole (BTA) derivatives were synthesized as tyrosine protein kinase inhibitors using fragment-based design strategy. All desired compounds were synthesized with the reaction of benzotriazole, chloroacetonitrile and aromatic aldehyde using Ultrasonic-Microwave method and characterized by IR, ¹H and ¹³C-NMR, mass spectrometry (MS) and elemental analysis. The anticancer activity of these compounds was evaluated by CCK-8 method against carcinoma VX2, lung cancer A549, stomach cancer cell lines MKN45 and MGC in vitro. The results showed that all compounds showed good antiproliferative activity. In particular, compound 2.1 showed the most prominent inhibition of VX2 cell lines with IC₅₀ of 3.80 ± 0.75 μM. Compound 2.2 exhibited highly potent anticancer activity of stomach MGC cell lines with IC₅₀ of 3.72 ± 0.11 μM. A549 and MKN45 cell lines were sensitive to compound 2.5 with IC₅₀ of 5.47 ± 1.11 and 3.04 ± 0.02 μM, respectively.     

Nitrostyrene Derivatives of Adenosine 5′-Glutarates Modified with an Alkyl Spacer and their inhibitory activity on epidermal growth factor receptor protein tyrosine kinase

β-Nitrostyrene derivatives of adenosine 5′-glutarates are potent and selective bisubstrate-type inhibitors of the epidermal growth factor receptor protein tyrosine kinase (EGF-R PTK). In an attempt to improve the inhibitory activity, this type of compounds was modified with alkyl spacers of varying length between the nitrostyrene and the glutaryl units. The spacers consisted of 1, 3, 4, and 5 atoms to give compounds of the benzyl, oxyethyl, oxypropyl, and oxybutyl series, respectively (Schemes 1 and 2). Adenosine 5′-esters were prepared in the benzyl and oxypropyl series only. Compared to the compounds in the parent series without spacer (IC₅₀ = 0.7–12 μM ), most of the modified compounds inhibited the EGF-R PTK only marginally or were inactive (IC₅₀ ≥ 100 μM ). The only exceptions were the free acids 19 and 20 with IC₅₀ values of ca. 5 μM . It is noteworthy that esterification of these two hydrogen glutarates with either MeOH or adenosine yielded inactive compounds, which is in contrast to the corresponding substances without spacers.     

Benzoylquinazolinone derivatives as new potential antidiabetic agents: α-Glucosidase inhibition,kinetic, and docking studies

Benzoylquinazolinone derivatives 3a–n were synthesized via a simple one-step reaction, and evaluated for in vitro α-glucosidase inhibitory activity. Compounds 3d , 3f–g , 3i , and 3m–n showed more inhibitory activity than standard drug acarbose (IC₅₀ = 750.0 ± 1.5 μM), and among them, compound 3d displayed the highest α-glucosidase inhibitory activity (IC₅₀ = 261.6 ± 0.1 μM). The kinetic analysis of the compound 3d revealed that this compound inhibited α-glucosidase in a competitive manner (K_i = 255 μM). The docking studies were applied to predict binding modes of the synthesized compounds in active site of α-glucosidase.     

Studies on 1, 2, 4-Benzothiadiazine 1, 1-Dioxide IX.1 Synthesis and Pharmacological Evaluation of 1, 2, 4-Benzothiadiazine 1, 1-Dioxide Biphenyl Tetrazoles as Angiotensin II Antagonists

In the course of our investigations on the development of cardiovascular agents, 3-butyl-2-[2′-(2H-tetrazol-5-yl)bipheny]-4-yl]methyl-2H-1, 2, 4-benzothiadiazine 1, 1-dioxide ( 2 ) was considered as a potential angiotensin II antagonist on the basis of bioisosteric replacement of the quinazoline ring of compound 1 with a 1, 2, 4-benzothiadiazine 1, 1-dioxide ring system. Alkylation of 6 with 4 afforded 7 and 8 in 24% and 28% yields, respectively. An attempt to remove the trityl group of compounds 7 and 8 under acidic condition gave the ring opened products 9 and 11 in 28% and 36% yields, respectively. However, compounds 2 and 10 were obtained in 46% and 85% yields when compounds 7 and 8 were refluxed in methanol. Preliminary assays of compounds 9 and 11 against angiotensin II receptors revealed weak activity with IC₅₀ values of 3.6 μM and 5.4 μM, respectively. Compound 10 (IC₅₀ = 87 nM) exhibited stronger binding affinity than compound 2 (IC₅₀ = 750 nM).     

The inhibition profiles of 4'-acylpyrrole–5-fluoroindolin-2-ones with a C-3' side chain for VEGFR2, PDGFR-β, and FGFR-1 protein kinases

In this study, we reported the inhibition profiles of 4′-acylpyrrole–5-fluoroindolin-2-one 3 with a C-3′ side chain for VEGFR2, PDGFR-β, and FGFR-1 protein kinases. The pyrrole-fused cyclohexanone moiety provided 3 with the best potency to inhibit the three kinases, and the C-3′ side chains contributed to the different inhibition profiles of 3 . Compound 3b with a C-3′ 2-carboxylethyl side chain showed good potency for the three kinase (IC₅₀: 25–260 nM), and compound 3g with a N,N-dialkyl-2-carbamoylethyl side chain was more active for VEGFR2 (IC₅₀: 59 nM) and PDGFR-β (IC₅₀: 16 nM) than FGFR-1 (IC₅₀: 1.7 μM). The C-3′ 3-(dialkylamino)propyl side chain accomplished 3h – j as selective PDGFR-β inhibitors (IC₅₀: 7.8–13 nM). Compound 3b was further investigated and found potent to inhibit VEGF- and FGF-dependent cell proliferation with moderate in vivo anticancer activity. Results from docking simulations revealed that the interactions of 3b with VEGFR2 and FGFR-1 which could account for the different inhibition profiles of 3 .     

Influence of Halogen Substitution in the Ligand Sphere on the Antitumor and Antibacterial Activity of Half‐sandwich Ruthenium(II) Complexes [RuX(η6‐arene)(C5H4N‐2‐CH=N‐Ar)]+

New complexes [(η⁶‐p‐cymene)Ru(C₅H₄N‐2‐CH=N–Ar)X]PF₆ [X = Br ( 1 ), I ( 2 ); Ar = 4‐fluorophenyl ( a ), 4‐chlorophenyl ( b ), 4‐bromophenyl ( c ), 4‐iodophenyl ( d ), 2,5‐dichlorophenyl ( e )] were prepared, as well as 3a – 3e (X = Cl) and the new complexes [(η⁶‐arene)RuCl(N‐N)]PF₆ (arene = C₆H₅OCH₂CH₂OH, N‐N = 2,2′‐bipyridine ( 4 ), 2,6‐(dimethylphenyl)‐pyridin‐2‐yl‐methylene amine ( 5 ), 2,6‐(diisopropylphenyl)‐pyridin‐2‐yl‐methylene amine ( 6 ); arene = p‐cymene, N‐N = 4‐(aminophenyl)‐pyridin‐2‐yl‐methylene amine ( 7 )]. X‐ray diffraction studies were performed for 1a , 1b , 1c , 1d , 2b , 5 , and 7 . Cytotoxicities of 1a – 1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco‐2) (IC₅₀: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC₅₀: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC₅₀: 60.6–439.8 μM), 3a – 3e were tested against HepG2 and Caco‐2, and 4 – 7 were tested against Caco‐2. 1 – 7 were tested against non‐cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5‐fluorouracil (5‐FU), but 3a – 3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC₅₀ than 5‐FU. Complexes with X = Br or I had moderate activity against Caco‐2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a , 2b , 3a , and 7 were tested against antibacterial susceptible and resistant Gram‐negative and ‐positive bacteria. 1a , 2b , and 3a showed activity against methicillin‐resistant S. aureus (MIC = 31–2000 μg · mL^–1).