Month: December 2022

Yamani, Abdellah published the artcileDiscovery and optimization of novel pyrazole-benzimidazole CPL304110 as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1-3), Application In Synthesis of 151-10-0, the main research area is pyrazolyl benzimidazole preparation antitumor docking FGFR inhibitor; Anti-tumor activity; FGFR (1–3) inhibitor; Pyrazole-benzimidazole.

The scaffolds hybridization approach, scaffold-hopping concept, has been employed to synthesize a series of novel pyrazole-benzimidazoles I [R1 = H, Cl; R2 = morpholin-4-yl, 4-methylpiperazin-1-ylcarbonyl, tetrahydropyran-4-ylcarbamoyl, etc.; R3 = H, F]. Compound I [R1 = R3 = H; R2 = 4-methylpiperazin-1-yl] (CPL304110) was identified as a selective and potent pan-FGFR inhibitor for FGFR1, FGFR2, FGFR3 with IC50 of 0.75 nM, 0.50 nM, 3.05 nM resp., and IC50 of 87.90 nM for FGFR4. Due to its favorable pharmacokinetic profile, low toxicity and potent anti-tumor activity in-vivo, this compound I is currently under evaluation in phase I clin. trial for the treatment of bladder, gastric and squamous cell lung cancers (01FGFR2018; NCT04149691).

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Application In Synthesis of 151-10-0.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Maadwar, Sasikala published the artcileA facile and an efficient synthesis of 3, 3-disubstituted oxindole scaffolds and their cytotoxic properties, Category: isoquinoline, the main research area is diphenyl indolinone preparation antitumor activity SAR.

3,3-Disubstituted oxindole derivatives I [R = H, Me, Cl, etc.; R1 = 1,2-dimethoxy, 1,3-dimethoxy, 1,4-dimethoxy, 1,3,5-trimethoxy] were synthesized by treating isatins with electron rich benzene derivatives at room temperature by using BF3·O(Et)2 as catalyst which reduced the synthesis time. The compounds I were evaluated for cytotoxic activity against human breast cancer cells (MCF7) and human ovarian carcinoma cells (SKVO3) by using MTT assay. Compounds I [R = Cl, Br; R1 = 1,3,5-trimethoxy] (7.2±0.22μM and 11.80.21±μM), 2(7.10.24±μM and 9.8±0.27μM), exhibited relatively higher cytotoxic activity against both MCF7 and SKVO3 cell lines, resp.

International Research Journal of Pharmacy published new progress about Antitumor agents. 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Gorle, Sridevi published the artcileSynthesis and anticancer activity of novel pyrazolo[4′,3′:5,6]pyrano[2,3-d] pyrimidin-5(2H)-one derivatives, Formula: C9H10O3, the main research area is pyrazolopyranopyrimidinone preparation antitumor SAR.

A novel sequence of pyrazole connected pyrano[2,3-d]-pyrimidin-5(2H)-ones, compounds I [R = 4-Me, 2-Cl, 2-Br, etc.] were designed, prepared and screened for their cytotoxicity against four human cancer cell lines like MCF-7 (breast), HeLa (cervical), CaCo2 (colorectal) and HepG2 (liver) by MTT assay. Most of the tested mols. were exhibited good to excellent cytotoxicity against all tested cell lines when compared to the standard drug Doxorubicin. Amongst all the synthesized target compounds, the mols. compounds I [R = 2,3,4-triMeO, 3,4,5-triMeO] exhibited the excellent anticancer activity against all the human MCF-7, HeLa, CaCo2 and HepG2 tumor cell lines, with the inhibitory concentration (IC50) values of 14, 14, 13, & 16μg mL-1 and 16, 14, 15 & 17μg mL-1, resp., while, compounds I [R = 2,3-diMeO, 3,4-diMeO] revealed good inhibitory activity against all screened cell lines with the IC50 values of 22, 25, 25 & 24μg mL-1 and 21, 20, 21, & 20μg mL-1. All the novel target mols. were determined and characterized by various spectroscopic (1H NMR, 13C NMR and HR-MS) anal.

Chemical Data Collections published new progress about Antitumor agents. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, Formula: C9H10O3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

El-Kalyoubi, Samar A. published the artcileUracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline-Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors, Application of 1-Methylurea, the main research area is aminothioxo pyrimidinyliminomethyl quinolinone preparation carbonic anhydrase inhibition antitumor SAR; anticancer; carbonic anhydrase; quinoline; uracil; zinc-binding group.

A series of quinoline-uracil hybrids has been rationalized and synthesized. The inhibitory activity against hCA isoforms I, II, IX, and XII was explored. Compoundsmonstrated powerful inhibitory activity against all tested hCA isoforms. Compound (E)-6-Amino-5-(((6-methoxy-2-oxo-1,2-dihydroquinolin-3-yl)methylene)amino) pyrimidine-2,4(1H,3H)-dione displayed the best selectivity profile with good activity. Compound (E)-6-Amino-1-methyl-5-(((2-oxo-1,2-dihydroquinolin-3-yl)methylene)amino) pyrimidine-2,4(1H,3H)-dione displayed the best activity profile with minimal selectivity. Compound (E)-3-(((6-Amino-1-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5yl)imino)methyl)-6-methoxyquinolin-2(1H)-one emerged as the best congener considering both activity (IC50 = 140 and 190 nM for hCA IX and hCA XII, resp.) and selectivity (S.I. = 13.20 and 9.75 for II/IX, and II/XII, resp.). The most active hybrids were assayed for antiproliferative and pro-apoptotic activities against MCF-7 and A549. In silico studies, mol. docking, physicochem. parameters, and ADMET anal. were performed to explain the acquired CA inhibitory action of all hybrids. A study of the structure-activity relationship revealed that bulky substituents at uracil N-1 were unfavored for activity while substituted quinoline and thiouracil were effective for selectivity.

Pharmaceuticals published new progress about Antitumor agents. 598-50-5 belongs to class isoquinoline, name is 1-Methylurea, and the molecular formula is C2H6N2O, Application of 1-Methylurea.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Al Otaibi, Ahmed published the artcileA methanol and protic ionic liquid Ugi multicomponent reaction path to cytotoxic α-phenylacetamido amides, Computed Properties of 86-51-1, the main research area is protic ionic liquid alpha phenylacetamido amides anticancer.

The Ugi four component reaction of an aldehyde, amine, isocyanide and an ethanoic acid was effected smoothly in protic ionic liquids ethylammonium nitrate (EAN) and propylammonium nitrate (PAN) to afford analogs of α-phenylacetamido amides in good to excellent isolated yields. The corresponding reactions in [BMIM][PF6] and the protic ionic liquid ethanolammonium nitrate (ETAN) failed. Microwave irradiation in EAN facilitated rapid access to three focused libraries, based on the parent isocyanide: cyclohexyl isocyanide, benzyl isocyanide and Et isocyanoacetate. Anal. of the structure activity relationship data suggested the presence of a bulky moiety originating from the isocyanide (cyclohexyl and benzyl) enhanced cytotoxicity. Removal of the acetylenic H-atom from the ethanoic acid moiety was detrimental to cytotoxicity. The most active analogs produced, N-(2-cyclohexylamino)-1-(4-methoxyphenyl)-2-oxoethyl-N-(3,5-dimethoxyphenyl)propiolamide, returned average GI50 values of ≤1 μM across the cancer cell lines evaluated. Combined, these data suggest that analogs of this nature are interesting potential anti-cancer development leads.

RSC Advances published new progress about Antitumor agents. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, Computed Properties of 86-51-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Guan, Hong-Hsiang published the artcilePlumbagin, a Natural Product with Potent Anticancer Activities, Binds to and Inhibits Dihydroorotase, a Key Enzyme in Pyrimidine Biosynthesis, Name: 3,5-Diamino-1,2,4-triazole, the main research area is plumbagin anticancer agent dihydroorotase breast cancer; 4T1 cell; CAD; allantoinase; anticancer; crystal structure; dihydroorotase; dihydropyrimidinase; drug design; plumbagin; pyrimidine biosynthesis.

Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway for pyrimidine nucleotides, and an attractive target for potential anticancer chemotherapy. By screening plant extracts and performing GC-MS anal., we identified and characterized that the potent anticancer drug plumbagin (PLU), isolated from the carnivorous plant Nepenthes miranda, was a competitive inhibitor of DHOase. We also solved the complexed crystal structure of yeast DHOase with PLU (PDB entry 7CA1), to determine the binding interactions and investigate the binding modes. Mutational and structural analyses indicated the binding of PLU to DHOase through loop-in mode, and this dynamic loop may serve as a drug target. PLU exhibited cytotoxicity on the survival, migration, and proliferation of 4T1 cells and induced apoptosis. These results provide structural insights that may facilitate the development of new inhibitors targeting DHOase, for further clin. anticancer chemotherapies.

International Journal of Molecular Sciences published new progress about Antitumor agents. 1455-77-2 belongs to class isoquinoline, name is 3,5-Diamino-1,2,4-triazole, and the molecular formula is C2H5N5, Name: 3,5-Diamino-1,2,4-triazole.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Pereira, Daniela published the artcileDesign and synthesis of new inhibitors of p53-MDM2 interaction with a chalcone scaffold, Related Products of isoquinoline, the main research area is chalcone derivative anticancer agent p53 MDM2 interaction docking cancer.

The virtual screening of a library of chalcone derivatives led us to the identification of potential new MDM2 ligands. The chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53-MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two chalcones (3 and 4) were identified as putative small mol. inhibitors of p53-MDM2 interaction. The activity of both chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Addnl., chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-mol. inhibitor of p53-MDM2 interaction), chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53-MDM2 inhibitors.

Arabian Journal of Chemistry published new progress about Antitumor agents. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, Related Products of isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Xu, Geng published the artcileMitochondria-Targeted Triphenylphosphonium Conjugated C-3 Modified Betulin: Synthesis, Antitumor Properties and Mechanism of Action, Product Details of C9H10O3, the main research area is triphenylphosphonium conjugated betulin apoptosis cell cycle arrest antitumor; antiproliferation; betulin; conjugation; drug discovery; mitochondria; structure-activity relationship; triphenylphosphonium.

A series of mitochondria-targeted triphenylphosphonium conjugated C-3 modified betulin were synthesized and evaluated against tumor cells. As a result, a new derivative 13 i, the conjugate of 3-O-(3′-acetylphenylacetate)-betulin with triphenylphosphonium, was identified as the one with the best anti-tumor effect. Conjugate 13 i significantly inhibited HCT116 cells with IC50 at 0.66 μM. While betulin, C-3 modified betulin, and the triphenylphosphonium moiety showed no inhibition of HCT116 cell proliferation at 20 μM. More importantly, 13 i exhibited a more cytotoxic effect against the tumor cell HCT116 than normal cell NCM460. Mode of action studies demonstrated that 13 i induced the G2/M phase cell cycle arrest and apoptosis in HCT116 cells through the mitochondrial pathway. Structure-activity relationship anal. revealed that integration of triphenylphosphonium moiety into the C-28 of betulin can greatly improve cytotoxicity. Appropriate modification on C-3 of the conjugate would improve the selectivity.

ChemMedChem published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Product Details of C9H10O3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Hosseinzadeh, Leila published the artcileSynthesis of 4-phenyl-4,5-dihydropyranopyrazolone derivatives with activated potassium carbonate: evaluation of anticancer activity on cancer cell lines and apoptosis mechanism, Related Products of isoquinoline, the main research area is phenyl dihydropyranopyrazolone derivative potassium carbonate apoptosis anticancer activity.

A green and efficient one-pot, four-component synthesis of 4-phenyl-4,5-dihydropyranopyrazolone derivatives 5a-5l is described in ethanol-water with activated potassium carbonate and evaluation of anticancer activity on cancer cell lines and apoptosis mechanism is also investigated. This method provides several advantages such as environmental friendliness, shorter reaction time, excellent yields, and simple workup procedure. The in vitro cytotoxic activity of the synthesized compounds was investigated against cancer cell lines (PC-3, MCF-7, and A-2780) in comparison with doxorubicin, a well-known anticancer drug, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide colorimetric assay. Also apoptosis studies were investigated by caspase-3 and caspase-9 enzymes and mitochondrial membrane potential. Our compounds showed acceptable and moderate cytotoxicity compared with doxorubicin in the studied cell lines. The compounds 5g in PC3 cell line (half maximal inhibitory concentration (IC50 = 104 μM)), 5g and 5i in MCF7 cell line (IC50 = 23 and 87 μM, resp.), and 5g-5i in A2780 cell line (IC50 = 60, 50, and 31 μM, resp.) showed the best results close to the control drug doxorubicin. The compound 5h showed significant result in the activation of caspase-3 and caspase-9 enzymes in comparison with the control. Only the 5g in MCF7 cells and the 5g-5i derivatives in A2780 cells caused increased mitochondrial membrane potential compared to the control group.

Journal of Reports in Pharmaceutical Sciences published new progress about Antitumor agents. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, Related Products of isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Chen, Qian published the artcileDesign and synthesis of novel nordihydroguaiaretic acid (NDGA) analogues as potential FGFR1 kinase inhibitors with anti-gastric activity and chemosensitizing effect, Application In Synthesis of 86-51-1, the main research area is gastric cancer FGFR1 NDGA growth survival migration; chemosensitizing effect; fibroblast growth factor receptor-1 inhibitor; gastric cancer; nordihydroguaiaretic acid analogues; synthesis.

Aberrant fibroblast growth factor receptor-1 (FGFR1), a key driver promoting gastric cancer (GC) progression and chemo-resistance, has been increasingly recognized as a potential therapeutic target in GC. Hereon, we designed and synthesized a series of asym. analogs using Af23 and NDGA as lead compounds by retaining the basic structural framework (bisaryl-1,4-dien-3-one) and the unilateral active functional groups (3,4-dihydroxyl). Thereinto, Y14 showed considerable inhibitory activity against FGFR1. Next, pharmacol. experiments showed that Y14 could significantly inhibit the phosphorylation of FGFR1 and its downstream kinase AKT and ERK, thus inhibiting the growth, survival, and migration of gastric cancer cells. Furthermore, compared with 5-FU treatment alone, the combination of Y14 and 5-FU significantly reduced the phosphorylation level of FGFR1, and enhanced the anti-cancer effect by inhibiting the viability and colony formation in two gastric cancer cell lines. These results confirmed that Y14 exerted anti-gastric activity and chemosensitizing effect by inhibiting FGFR1 phosphorylation and its downstream signaling pathway in vitro. This work also provides evidence that Y14, an effective FGFR1 inhibitor, could be used alone or in combination with chemotherapy to treat gastric cancer in the future.

Frontiers in Pharmacology published new progress about Antitumor agents. 86-51-1 belongs to class isoquinoline, name is 2,3-Dimethoxybenzaldehyde, and the molecular formula is C9H10O3, Application In Synthesis of 86-51-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem