Antitumor studies. Part 1: Design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents

Ali, Hamed I.; Tomita, Keiichiro; Akaho, Eiichi; Kambara, Hiroto; Miura, Shinji; Hayakawa, Hisao; Ashida, Noriyuki; Kawashima, Y.; Yamagishi, Takehiro; Ikeya, Hisao; Yoneda, Fumio; Nagamatsu, Tomohisa

doi:10.1016/j.bmc.2006.09.063

Cited by 54 publications

(18 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Molecular docking studies for binding to protein tyrosine kinase (PTK) showed low binding free energies (Δ G ) and K i values for several compounds, especially for 2‐deoxo‐2‐phenylflavin‐5‐oxides ( 22 ), which displayed Δ G values between −7.84 and −5.95 kcal/mol. The binding free‐energy levels correlated with the IC 50 values obtained against cancer cell lines …”

Section: Antitumor Activitymentioning

confidence: 84%

Therapeutic potential of pteridine derivatives: A comprehensive review

Carmona‐Martínez

Ruiz–Alcaraz

Vera

et al. 2018

Medicinal Research Reviews

View full text Add to dashboard Cite

Pteridines are aromatic compounds formed by fused pyrazine and pyrimidine rings. Many living organisms synthesize pteridines, where they act as pigments, enzymatic cofactors, or immune system activation molecules. This variety of biological functions has motivated the synthesis of a huge number of pteridine derivatives with the aim of studying their therapeutic potential. This review gathers the state‐of‐the‐art of pteridine derivatives, describing their biological activities and molecular targets. The antitumor activity of pteridine‐based compounds is one of the most studied and advanced therapeutic potentials, for which several molecular targets have been identified. Nevertheless, pteridines are also considered as very promising therapeutics for the treatment of chronic inflammation‐related diseases. On the other hand, many pteridine derivatives have been tested for antimicrobial activities but, although some of them resulted to be active in preliminary assays, a deeper research is needed in this area. Moreover, pteridines may be of use in the treatment of many other diseases, such as diabetes, osteoporosis, ischemia, or neurodegeneration, among others. Thus, the diversity of the biological activities shown by these compounds highlights the promising therapeutic use of pteridine derivatives. Indeed, methotrexate, pralatrexate, and triamterene are Food and Drug Administration approved pteridines, while many others are currently under study in clinical trials.

show abstract

Section: Antitumor Activitymentioning

confidence: 84%

Therapeutic potential of pteridine derivatives: A comprehensive review

Carmona‐Martínez

Ruiz–Alcaraz

Vera

et al. 2018

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…We investigated the AutoDock binding affinities of various structures for their potential protein tyrosine inhibitory activities, including: 2, 3, 4- trisubstitutred -1, 2-dihydropyrrolo[ 1,2-a ] [ 1, 3, 5 ]triazin derivatives Ia-k, 4-(3, 5-di-tert-butylphenylcarbamoyl)-2-amino benzoic acid, its 2-nitro benzoic acid, their methylester analogs IIa-d such as benzopyrido, benzopyrimido, benzopiprazino [1,4] dioxin-2-ol IIIa-c, dipyrido [1,4] dioxin-2-ol analogs IIId-g, 2-substituted-(6-fluoro-3,4-dihydro-4- substituted pheno-xypyrido [3,4-d] pyrimidin-2-yl) derivatives IVa-d, tyrosine containing di- or tripeptides Va-f, acetylated tyrosine containing tetrapeptides analogs Vg-m, deazapteridine-steroid hybrid compounds VIad, hybrid compounds possessing 5-deazapteridine and steroid in the same ring system [12], 2-deoxo-2-phenyl-5-deazaflavins VIIa-h [13, 14], 2-deoxo-2-piperidino-5-deazaflavin VIIi [15], 2-deoxo-2-morpholino-5- deazaflavin VIIj [15], 2-deoxo-2-phenylflavins VIIm-o, computationally newly designed 2-deoxo-2-glycino, 2-tyrosino, 2-histidino-N10- methylflavin-N-oxides VIIp-r, 5-deazaflavin derivatives VIIIa-c, N3- methyl-5-(monosubstituted alkylamino)-5-deazaflavin derivatives VIIId-g [14], computationally designed pyridodipyrimidines IXa-f [14], and bis- (5-deazaflavin-10-yl) alkanes Xa,b [14]. Additional structures obtained from Sumisho Data Base were studied, including abacavir, PB-01547328, PB-99211665, F0007-0958, OSSK-633719, OSSK-692604, 831, PB- 00623451, and compound 1505335.…”

Section: Resultsmentioning

confidence: 99%

“…The selective PKC inhibitory activities of 5-deazaflavins, 2-deoxy-2- phenyl-5-deazaflavins, {2-phenylpyrimido[4, 5-b]quinolin-4(10H)-ones}, and their effective growth inhibition against cancer cells such as the A431 cells, and HT1080 cells were reported [11]. Synthesis of the hybrid compounds, which structurally contain two different biologically or pharmacologically active compounds of 5-deazaflavins and steroids in the same ring system, were carried out by condensation of 6-(monosubstituted amino)uracils or 6-(monosubstituted amino)-2-phenylpyrimidin-4(3H)- ones with 2-hydroxy-methylene androstanolone or 2- hydroxymethylenetestosterone.…”

Section: Introductionmentioning

confidence: 99%

“…Steroid receptors may serve to localize and concentrate appended drug species, mainly in hormones responsive for the production of neoplastic cells. Moreover, 5-deazaflavins (5-deazaisoalloxazines) have greatly attracted our attention [13– 17]. Antitumor activities of nitro-5- deazaflavin-pyrrolecarboxamide hybrid molecules [18] and 5-amino-5- deazaflavin derivatives revealed potential inhibitory activities against L1210 or KB cells [19].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structure-based drug design and AutoDock study of potential protein tyrosine kinase inhibitors

Ali¹,

Nagamatsu²,

Akaho³

2011

Bioinformation

Self Cite

View full text Add to dashboard Cite

Different classes of compounds were investigated for their binding affinities into different protein tyrosine kinases (PTKs) employing a novel flexible ligand docking approach by using AutoDock 3.05 and 4. These compounds include many flavin analogs, which were developed in our group with varying degrees of cytotoxic activity (comparable or moderately superior to cisplatin and ara-c), and database selected analogs. They were docked onto twelve different families of PTKs retrieved from the Protein Data Bank. These proteins are representatives of plausible models of interactions with chemotherapeutic agents. A comparative study of the intact co-crystallized ligands of various types of PTKs was carried out. Results revealed that the new class of 5-deazapteridine and steroid hybrid compounds VIa,b, and d, and the vertical-type bispyridodipyrimidine with n-hexyl chain junction between its N-10 and N-10 atoms Xa, exhibited non-selective PTK binding capacities, with the lowest (Gb). On the other hand, 2-amino benzoic acid analog IIa, phenoxypyrido [3, 4-d]pyrimidine derivative IVc, tyrosine containing tripeptide Vd, and the one from Sumisho data base 831 are proposed to have selective PTK binding affinities to certain classes of tyrosine kinases, namely, HGFR (c-met), ZAP-70, insulin receptor kinase, EGFR, respectively. All These compounds of highest affinities were docked within the binding sites of PTKs with reasonable RMSD and 1-5 hydrogen bonds.

show abstract

“…Also the formation of more and/or tighter hydrogen bonds provides higher binding affinities. 22,23 The pyrimidone derivatives 7a,b and 8a-c were deeply embedded into CDK2 binding site displayed ∆G b between -8.31 and -10.81 kcal/mol. Compounds 7a,b and 8c bound to the active site of CDK2 through 2 hydrogen bonds with Leu 83, whereas compound 8b showed 2 hydrogen bonds with Asp145 and Asn132.…”

Section: Docking Studymentioning

confidence: 99%

Synthesis of Potent Anticancer Thieno[2,3-d]Pyrimidine Derivatives

Kandeel

Mounir

Refaat

et al. 2012

Journal of Chemical Research

View full text Add to dashboard Cite

As part of our program to identify novel cytotoxic agents, various series of hexahydrocycloocta [4,5]thieno [2,3-d] pyrimidines and pyrimidin-4-ones substituted by aryl at the C-2 position together with phenylethylamino, substituted amino, hydrazinyl or arylidenhydrazinyl substituents at the C-4 position were synthesised. These compounds were prepared as bioisosteres of gefitinib, an antitumour drug used for the treatment of gastrointestinal stromal tumours. All compounds exhibited antitumour activity against (HCT 116) cell line in vitro. Eight compounds (IC 50 : 3.89, 4.65, 6.63, 6.94, 7.89, 9.53,12.00 and 12.30 µg mL −1 , respectively) exhibited 4.3 to 1.3 fold more potent antitumour activity than imatinib (IC 50 : 16.93 µg mL −1 ). Also, a docking study of the newly synthesised compounds with the active site of CDK2 was described.

show abstract

Antitumor studies. Part 1: Design, synthesis, antitumor activity, and AutoDock study of 2-deoxo-2-phenyl-5-deazaflavins and 2-deoxo-2-phenylflavin-5-oxides as a new class of antitumor agents

Cited by 54 publications

References 14 publications

Therapeutic potential of pteridine derivatives: A comprehensive review

Therapeutic potential of pteridine derivatives: A comprehensive review

Structure-based drug design and AutoDock study of potential protein tyrosine kinase inhibitors

Synthesis of Potent Anticancer Thieno[2,3-d]Pyrimidine Derivatives

Contact Info

Product

Resources

About