A 3-D (3,5)-connected Cd coordination framework with unique twofold interpenetrating (4·6)(4·6·8) network topology

Assembly of N,N′-bis(4-picolinoyl)hydrazine (H₂L) with cadmium nitrate in the presence of dicyanamide anion (dca) affords a new coordination polymer {[Cd(HL)(dca)] · (H₂O)_0.5}_n (1), in which the [Cd(HL)]_n layers are extended by dca bridges to result in a three-dimensional (3-D) coordination framework. The network structure of 1 has unusual (3,5)-connectivity and represents a new type of (4·6²)(4·6⁶·8³) topology. Two such identical and complementary networks are entangled to generate a twofold parallel interpenetrating supramolecular lattice.     

Efficient synthesis and biological evaluation of 1,2,9-trisubstituted 1,9-dihydro-6H-purin-6-ones

The carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aromatic isocyanates, reacted with amines in the presence of a catalytic amount of RO^?Na⁺ to give the 1,2,9-trisubstituted 1,9-dihydro-6H-purin-6-ones 6 in good yields. Compound 6 exhibited cytotoxicity against various cancer cells. For example, compounds 6b showed the best inhibition activities against KB, HepG2 and OVCAR3 with IC₅₀ 9.5, 20.4 and 10.0 μM.     

Syntheses of 6-(2-hydroxy-6-phenylhexyl)-5,6-dihydro-2H-pyran-2-one derivatives and their cytotoxicities

The cytotoxicities against cancer cells (HL-60, HeLa) and insect cells (Sf9) of four stereoisomers of 6-(2-hydroxy-6-phenylhexyl)− 5,6-dihydro-2H-pyran-2-one (1) were evaluated, and then their structure-activity relationships examined. The 2′-dehydroxy derivative 5 of (6 R,2′R)- and (6 R,2′S)-1 showed the highest activity against HeLa cells (IC₅₀ = 1.4 μM). To evaluate the effect of the 2′-hydroxy group of 1, 6R-and 6S-oxetane derivatives were also synthesized and their activities examined. Against HeLa and HL-60 cells, the activities of the less potent stereoisomers were enhanced 3–4-fold by the introduction of the oxetane moieties at the 2′-position. Against the insect cell line (Sf9), phenyl derivative 7 showed the highest activity with an IC₅₀ value of 8.0 μM.     

Semi-synthetic antibiotics: Titanium(IV), zirconium(IV) and mercury(II) complexes of 6-amino penicillinic acid

A number of organometallic derivatives involving 6-amino penicillinic acid (I), of the types η⁵-R)₂M- (Cl)L^?Et₃NH⁺ (II), (η⁵-R)₂M(Cl)L (III) and R′HgL [R = cyclopentadienyl (C₅H₅), indenyl (C₉H₇), R′ = phenyl (C₆H₅), p-acetoxyphenyl (p-CH₃COOC₆H₄), o-hydroxyphenyl (o-HOC₆H₄), p-hydroxyphenyl (p-HOC₆H₄); M = Ti(IV), Zr(IV); LH = 6-amino penicillinic acid] have been synthesized and characterized. Conductance measurements indicate that while the (η⁵-R)₂M(Cl)L^?Et₃NH⁺ complexes are 1:1 electrolytes, the remaining compounds are non-electrolytes. From IR and UV spectral studies it is concluded that the penicillin moiety is bidentate. PMR and CMR studies support the stoichiometry of the complexes. Fluorescence studies have been carried out for o- and p-HOC₆H₄HgL complexes and relevant photochemical parameters have been elucidated. X-ray diffraction studies have been made for the o-HOC₆H₄HgL complex. For the C₆H₅HgL, p-CH₃COOC₆H₄HgL and p-HOC₆H₄HgL complexes, thermal studies (TG and DTA) have been carried out and kinetic parameters for thermal degradation have been enumerated. In addition, the fragmentation pattern of these complexes has been analysed on the basis of mass spectra. The C₆H₅HgL and p-CH₃COOC₆H₄HgL complexes show positive bactericidal activities.     

Synthesis and antitubercular evaluation of novel substituted aryl and thiophenyl tethered dihydro-6H-quinolin-5-ones

A series of novel aryl and thiophenyl tethered dihydro-6H-quinolin-5-ones have been synthesized in very good yields through CeCl₃·7H₂O-NaI catalyzed one-pot condensation of β-enaminones derived from the respective methyl ketones; 1,3-cyclohexanedione & 5,5-dimethyl-1,3-cyclohexanedione and ammonium acetate refluxing in 2-propanol. Dihydro-6H-quinolin-5-ones 3a-f was further derivatized to the respective hydroxymethyl analogs using proline as an organocatalyst in aqueous media. Among the all 18 compounds screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H₃₇Rv (MTB), dihydro-6H-quinolin-5-ones 4e and 4f were found to be most active with MIC 3.13 μg/mL.     

A series of d transition metal coordination complexes: Structures and comparative study of surface electron behaviors (n = 9, 8, 7, 6, 5)

Ten transition metal coordination complexes [Cu₂(phen)(p-tpha)(μ-O)]_n1, [Cu(m-tpha)(imH)₂]_n2, [Ni(5-Haipa)₂(H₂O)₂]_n3, [Ni(phen)₂(H₂O)₂]·btc·[Ni(H₂O)₆]_0.5·9H₂O 4, [Co(2,5-pdc)(H₂O)₂]_n·nH₂O 5, [Co₂(2,5-pdc)₂(H₂O)₆]_n·2nH₂O 6, [Fe(2,5-Hpdc)₂(H₂O)₂]·H₂O 7, [Co(C₆H₄NO₂)₃]·H₂O 8, [Fe₂(μ₂-btec)(μ₂-H₂btec)(bipy)₂(H₂O)₂]_n9, [Mn(phen)(2,5-pdc)(H₂O)₂]·H₂O 10 (H₄btec = 1,2,4,5-benzenetetracarboxylic acid, phen = 1,10-phenanthroline, 2,5-H₂pdc = 2,5-pyridine-dicarboxylic acid, p-tpha = p-phthalic acid, m-tpha = m-phthalic acid, bipy = 2,2′-bipyridine, 5-H₂aipa = 5-aminoisophthalic acid, imH = imidazole, H₃btc = 1,3,5-benzenetricarboxylic acid) were synthesized through hydrothermal method. They were characterized by UV-Vis absorption spectra, single-crystal X-ray diffraction and surface photovoltage spectra (SPS). Structural analysis indicated that the complexes 1, 2, 3, 5, 6 and 9 were linked into infinite structures bridged by organic acid ligands. The other four complexes were molecular complexes and further connected to 2D or 3D structures by the hydrogen bonds. The SPS of complexes 1-10 indicate that there are positive response bands in the range of 300-800 nm showing different levels of photo-electric conversion properties. The intensity, position, shape and the number of the response bands in SPS are obviously different since the structure, species, valence, dⁿ electrons configuration and coordinated environment of the center metals are different. There are good relationships between SPS and UV-Vis spectra.     

Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel 1-(1H-benzimidazol-6-yl)pyridin-2(1H)-one derivatives and design to avoid CYP3A4 time-dependent inhibition

Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that structurally featured an imidazo[1,2-a]pyridine-based bicyclic motif. To investigate imidazopyridine variants with lower basicity and less potential to inhibit cytochrome P450 3A4 (CYP3A4), we designed pyridine-2(1H)-ones bearing various less basic bicyclic motifs. Among these, a lead compound 6a bearing a 1H-benzimidazole motif showed comparable binding affinity to MCHR1 to the corresponding imidazopyridine derivative 1. Optimization of 6a afforded a series of potent thiophene derivatives (6q–u); however, most of these were found to cause time-dependent inhibition (TDI) of CYP3A4. As bioactivation of thiophenes to form sulfoxide or epoxide species was considered to be a major cause of CYP3A4 TDI, we introduced electron withdrawing groups on the thiophene and found that a CF₃ group on the ring or a Cl adjacent to the sulfur atom helped prevent CYP3A4 TDI. Consequently, 4-[(5-chlorothiophen-2-yl)methoxy]-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (6s) was identified as a potent MCHR1 antagonist without the risk of CYP3A4 TDI, which exhibited a promising safety profile including low CYP3A4 inhibition and exerted significant antiobesity effects in diet-induced obese F344 rats.     

2-Phenyl-9H-purine-6-carbonitrile derivatives as selective cathepsin S inhibitors

Starting from previously disclosed equally potent cathepsin K and S inhibitor 4-propyl-6-(3-trifluoromethylphenyl)pyrimidine-2-carbonitrile 1, a novel 2-phenyl-9H-purine-6-carbonitrile scaffold was identified to provide potent and selective cathepsin S inhibitors.     

Synthesis and in vitro anti-hepatitis B virus activity of 6H-[1]benzothiopyrano[4,3-b]quinolin-9-ols

A series of novel 6H-[1]benzothiopyrano[4,3-b]quinoline derivatives were prepared and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in human hepatoblastoma-derived liver Hep-G2 cells. Compounds 10g, 10h, 10j, 10l and 10o were found to be potent anti-HBV compounds with IC₅₀ values less than 50 μM. The most promising compound was 10l, with an IC₅₀ value of 14.7 μM and a SI value of 12.4. This is the first report of the anti-HBV effects of 6H-[1]benzothiopyrano[4,3-b] quinolin-9-ols.     

Synthesis of 2- (and 6-) -dithian-2-yluracil nucleosides and their conversion into nucleoside derivatives

Addition of 2,2′-anhydro-[1-(3-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)uracil] (1) to excess 2-litho-1,3-dithiane (2)in oxolane at ?78° gave 2-(1,3-dithian-2-yl)-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)pyrimidinone (3), O²,2′-anhydro-5,6-di-hydro-6-(S)-(1,3-dithian-2-yl)-5′-O-trityluridine (4), and 2-(1,4-dihydroxybutyl)-1,3-dithiane (5) in yields of 15, 30, and 10% respectively. The structure of 3 was proved by its hydrolysis in acid to give 2-(1,3-dithian-2-yl)-4-pyrimidinone (6) and arabinose, and by desulfurization with Raney nickel to yield the known 2-methyl-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)-pyrimidinone (7). Detritylation of 3 without glycosidic cleavage could only be effected by prior acetylation to 1-(2,3-di-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)-2-(1,3-dithian-2-yl)-4(1H)-pyrimidinone (8) which, after treatment with acetic acid at room temperature for 65 h followed by the action of sodium methoxide gave 2-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyl-4(1H)-pyrimidinone (10) in 45% yield. Detritylation of 4 in boiling acetic acid gave 5,6-dihydro-6-(S)-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyluracil (12) and 3-[(S)-1-(1,3-dithian-2-yl)]propionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (13) in 10 and 90% yields, respectively. When 12 was kept in water or methanol for 7 days, quantitative conversion into 13 occurred. Acid hydrolysis of 12 afforded arabinose and 5,6-di-hydro-6-(1,3-dithian-2-yl)uracil (14), which was desulfurized with Raney nickel to the known 5,6-dihydro-6-methyluracil (15). Treatment of 13 with trifluoroacetic anhydride-pyridine yielded 77% of the cyano derivative 17. Similar dehydration of 3-(R)-1-methylpropionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxalidinone (18), obtained by desulfurization of 13, gave 60% of the nitrile 19. Hydrogenation of 19 over platinum oxide in acetic anhydride gave the acetamide derivative 20 in 95% yield. Nitrobenzoylation of 13 gave 3-[(S)-1-(1,3-dithian-2-yl)]cyanomethyl-3,5-di-O-p-nitrobenzoyl-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (22), which was converted in 37% yield by treatment with methyl iodide in dimethyl sulfoxide into the aldehyde 24, characterized as the semicarbazone 25. The purification of 5 and its characterization as 2-(1,4-di-O-p-nitrobenzoylbutyl)-1,3-dithiane (27) is described.     

Reactions of rhodium(II) and iridium(III) complexes bearing a P,O-coordination with tetracyanoethylene in the presence of KPF6

Reactions of Cp*M(MDMPP-P,O)Cl (1a: M=Rh, 1b: M=Ir; MDMPP-P,O=PPh₂(2-O-6-MeOC₆H₃)) with tetracyanoethylene (tcne) in the presence of KPF₆ gave Cp*MCl[PPh₂{2-O-3-(C(CN)₂CH(CN)₂)-6-MeOC₆H₂}] (2), [{Cp*MPPh₂{2-O-3-(C(CN)C(CN)₂)-6-MeOC₆H₂}}₂(CN)](PF₆) (3), [{Cp*IrPPh₂{2-O-3-(C(CN)C(CN)₂)-6-MeOC₆H₂}}(CN){Cp*Ir(MDMPP-P,O)}](PF₆) (4b) and [{Cp*Ir(MDMPP-P,O)}₂(CN)](PF₆) (5b), depending on the reaction conditions. Reaction of 2 with KPF₆ or AgOTf in the absence and presence of xylyl isocyanide (XylNC) gave 3 or [Cp*MCl{PPh₂(2-O-3-(C(CN)₂-CH(CN)₂)-6-MeOC₆H₂)}(XylNC)](OTf) (6). The structure of 3a (M=Rh) was confirmed by X-ray crystal analysis.     

6-Methoxyflavonols from the aerial parts of Tetragonia tetragonoides (Pall.) Kuntze and their anti-inflammatory activity

Dried aerial parts of Tetragonia tetragonoides were extracted with 70% EtOH, and the evaporated residue was successively separated into EtOAc, n-BuOH, and H₂O fractions. As a result of repeated SiO₂, ODS, and Sephadex LH-20 column chromatography, four new 6-methoxyflavonol glycosides (2–4, 8) along with four known ones (1, 5–7) were isolated. Several spectroscopic data led to determination of chemical structures for four new 6-methoxyflavonol glycosides (2–4, 8) and four known ones, 6-methoxykaempferol 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl-7-O-(6‴′-(E)-caffeoyl)-β-d-glucopyranoside (1), 6-methoxyquercetin (5), 6-methoxykaempferol (6), and 6-methoxykaempferol 7-O-β-d-glucopyranoside (7). Methoxyflavonol glycosides 2–8 also have never been reported from T. tetragonoides in this study. 6-Methoxyflavonols 5 and 6 showed high radical scavenging potential in DPPH and ABTS test. Also, all compounds showed significant anti-inflammatory activities such as reduction of NO and PGE₂ formation and suppression of TNF-α, IL-6, IL-1β, iNOS, and COX-2 expression in LPS-stimulated RAW 264.7 macrophages. In general, the aglycones exhibited higher activity than the glycosides. In addition, quantitative analysis of 6-methoxyflavonols in the T. tetragonoides aerial parts extract was conducted through HPLC.     

Synthesis of novel 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitrile derivatives as antimicrobial and antioxidant agents

As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2a–i), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5a–i), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6a–i) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7a–i). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe³⁺) reducing antioxidant power (FRAP) and metal chelating activity.     

New aryl phosphinite ligands avoiding ortho-metallation: Synthesis and molecular structures of trans-[PdCl2(PPh2OR)2] and trans-[Rh(CO)Cl(PPh2OR)2] (R = 2,4,6-Me3C6H2; 2,6-Ph2C6H3)

The new aryl phosphinites PPh₂OR (R = 2,4,6-Me₃C₆H₂, 1; R = 2,6-Ph₂C₆H₃, 2) have been prepared from chlorodiphenylphosphine and the corresponding phenols. In these ligands, the ortho-positions of the aromatic phosphite function are blocked by methyl and phenyl substituents, which allows coordination to metal centres without ortho-metallation. Thus, reaction with [PdCl₂(cod)] leads to the complexes trans-[PdCl₂(PPh₂OR)₂] (R = 2,4,6-Me₃C₆H₂, 3; R = 2,6-Ph₂C₆H₃, 4), while the reaction with [Rh₂(CO)₄Cl₂] gives trans-[Rh(CO)Cl(PPh₂OR)₂] (R = 2,4,6-Me₃C₆H₂, 5; R = 2,6-Ph₂C₆H₃, 6). The single-crystal X-ray structure analyses of 3 and 5 confirm the trans-coordination of the new ligands in these square-planar complexes.     

Synthesis, characterization and bioactivity of a novel 18-metallacrown-6: [Mn(pcshz)(CH3OH)]6 · 4CH3OH · 4H2O

The reaction of N-propionyl-5-chlorosalicylhydrazide (H₃pcshz) with Mn(OAc)₂ · 4H₂O in methanol solution gives a novel 18-metallacrown-6 [Mn(pcshz)(CH₃OH)]₆ · 4CH₃OH · 4H₂O (1). The structure of 1 has been determined by X-ray diffraction and it crystallizes in the monoclinic system and space group P2(1)/n. The ring of the metallacrown is consisted of six interlink [Mn-N-N] repeated units through hydrazide N-N group bridging the ring manganese ions. And the ligand enforces the metal ions to form the stereochemistry as a propeller configuration with alternation Λ/Δ form. The largest diameters of the disc-shaped hexanuclear ring are about 8.82 Å at entrance, 9.83 Å at the central of the cavity, respectively. The solution integrity and stability of the metallacrown was studied by electrospray ionization (ESI)-MS and UV-Vis spectroscopy. The results show it is soluble and stable in methanol. Antibacterial screening data indicate the forming of the complex weakens dramatically the antibacterial activity of the ligand H₃pcshz except for Eschericha coli.     

Synthesis and characterization of Fe(III)(3-CH3O-qsal)2PF6 · nH2O (n = 0, 2)

Compounds Fe^III(3-CH₃O-qsal)₂PF₆ · nH₂O (n = 0, 2) (1, 1 · 2H₂O) were synthesized and characterized: the structure of 1 and the magnetic properties of both compounds were determined. Compound 1 · 2H₂O presents properties characteristic of high-spin Fe(III), while 1 presents properties of low-spin Fe(III) with an onset of a gradual spin crossover at ca. 300 K.     

The monoamine oxidase inhibition properties of C6-mono- and N3/C6-disubstituted derivatives of 4(3H)-quinazolinone

Parkinson’s disease is characterised by the death of the nigrostriatal neurons and depletion of striatal dopamine. The standard symptomatic therapy consists of dopamine replacement with l-dopa, the metabolic precursor of dopamine, which represents the most effective treatment. Since monoamine oxidase (MAO) B is a key dopamine metabolising enzyme in the brain, MAO-B inhibitors are often used as adjuvants to l-dopa. In addition to the symptomatic benefits offered by MAO-B inhibitors, these drugs may also possess neuroprotective properties and possibly delay the progression of Parkinson’s disease. Based on the therapeutic use of MAO-B inhibitors, the present study evaluates a series of mono- and disubstituted derivatives of 4(3H)-quinazolinone as potential inhibitors of recombinant human MAO-A and MAO-B. Twelve C6-monosubstituted and nine N3/C6-disubstituted 4(3H)-quinazolinone derivatives were synthesised, which led to the discovery of novel quinazolinone derivatives with micromolar and submicromolar activities as inhibitors of MAO-B. The most potent mono- and disubstituted derivatives exhibited IC₅₀ values of 6.35 μM (7f) and 0.685 μM (8b), respectively. This study identifies suitable substitution patterns for the design of 4(3H)-quinazolinone derivatives as MAO-B inhibitors.     

Synthesis of new organotitanium (IV) complexes Cp2Ti(SeR)2 and Cp2TiCl(SeR) via tandem reactions involving `Cp2Ti' intermediate. Crystal structures of Cp2TiCl(SeR) (R=p-ClC6H4, p-BrC6H4)

A simple and convenient route for synthesizing organotitanium (IV) complexes with a general formula Cp₂Ti(SeR)₂ or Cp₂TiCl(SeR) has been developed. This synthetic route includes reduction of Cp₂TiCl₂ with Mg and an in situ treatment of the intermediate `Cp₂Ti' with diselenides RSeSeR. Interestingly, while the route involving reaction of Cp₂TiCl₂, Mg and RSeSeR in a molar ratio of 1:1:1 produced Cp₂Ti(SeR)₂, (1-5, R=α-C₁₀H₇, o-MeC₆H₄, m-MeC₆H₄, p-ClC₆H₄, p-BrC₆H₄) in 91-97% yields, the route involving reaction of Cp₂TiCl₂, Mg and RSeSeR in a molar ratio of 1: 0.5: 0.5 afforded Cp₂TiCl(SeR) (6-7, R=p-ClC₆H₄, p-BrC₆H₄) in 70% and 92% yields, respectively. 1-7 are new and have been characterized by elemental analysis and spectroscopy, as well as by X-ray diffraction analysis for 6 and 7. A possible pathway for production of these two types of organotitanium (IV) complexes, mainly depending upon the molar ratio of the starting materials, are briefly discussed.     

Design,synthesis and antiproliferative activity of novel substituted 2-amino-7,8-dihydropteridin-6(5H)-one derivatives

Based on our previous work, a series of novel 2-amino-7,8-dihydropteridin-6(5H)-one derivatives were designed and synthesized via a ring-closing strategy. Biological evaluation with four human cancer cell lines (BT549, T47D, MDA-MB-468, and MDA-MB-231) showed that most of these compounds possessed moderate to potent antiproliferative activities. The most promising compound 8-benzyl-2-(phenethylamino)-7,8-dihydropteridin-6(5H)-one (6q) possessing IC₅₀ values of 7.75, 6.37, and 10.73 μM against MDA-MB-468, T47D, and BT549, respectively, which were 49, 11, and 8 folds more active than the positive control fluorouracil. Moreover, fluorescence-activated cell sorting analysis revealed that compound 6q displayed a significant effect on G1 cell-cycle arrest in a concentration-dependent manner in T47D cells. The initial structure–activity relationship studies indicated that linker-length of amine chain in C-2 position of pyrimidine ring played a crucial role in modulating the antitumor activity, which could be of help in the rational design of dihydropteridin-6(5H)-ones as novel anticancer drugs.