Day: December 6, 2022

Li, Xinyu published the artcileSynthesis and biological evaluation of 3-aryl-quinoline derivatives as anti-breast cancer agents targeting ERα and VEGFR-2, Related Products of isoquinoline, the main research area is antitumor arylquinoline estrogen receptor alpha VEGFR 2 multi target; arylquinoline SAR anti breast cancer multi target; Anti-breast cancer; Estrogen receptor; Multi target; VEGFR-2.

Selective estrogen receptor modulators(SERMs) are a series of important small mol. compounds to modulate the estrogen receptor, such as tamoxifen. Although these drugs have shown great benefits in the treatment of breast cancer, the risk of endometrial cancer and endocrine resistance restrict their use. The reasonable designing of multi-target drugs can decrease the side effects and improve the tolerance of antineoplastic agents. Studies have identified that VEGFR-2 plays a pivotal role in tumor angiogenesis and drug resistance. Besides, a combination of Tamoxifen and a low dose of a VEGFR-2 inhibitor was reported to maximize therapeutic efficacy as well as to retard SERM resistant tumor growth. In this work, a series of 3-aryl-quinoline derivatives were designed to target ERα and VEGFR-2 to eliminate the disadvantages of SERMs. We identified that compounds I [R1 = H, R2 = MeO; R1 = MeO, R2 = H] displayed highly ER binding affinities as well as relative intensity VEGFR-2 inhibitory activities. Moreover, these two compounds exhibited excellent anti-proliferative activities against MCF-7 and HUVEC cell lines with low micromolar IC50 (1-8 μM). A further study confirmed that compound I [R1 = MeO, R2 = H] can reduce the expression of PgR mRNA, arrest cell cycle in MCF-7 breast cancer cells, and restrain the cell migration. Overall, based on the biol. activities data, I [R1 = MeO, R2 = H] can be chosen as a potential anti-cancer lead compound for further studying.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Related Products of isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Dong, Junmin published the artcileDesign, synthesis and biological evaluation of exiguamine A analogues as IDO1 inhibitors, Computed Properties of 86-51-1, the main research area is exiguamine A preparation SAR mol docking antitumor indoleamine dioxygenase; Cancer immunotherapy; Exiguamine A; Indoleamine 2,3-dioxygenase 1.

A series of exiguamine A analogs were designed and synthesized via 15 steps. Their inhibitory activities against IDO1 were tested and the structure-activity relationships were studied. Most compounds exhibited potent IDO1 inhibitory activities with IC50 values at the level of 10-7-10-8 M. Compound I was the most potent IDO1 inhibitor with an IC50 value of 65.3 nM, which was comparable with the pos. control drug epacadostat (IC50 = 46 nM). Moreover, compound I showed higher selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO) and no cytotoxicity at its effective concentration, rending it justifiable for further optimization and evaluation.

European Journal of Medicinal 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, Computed Properties of 86-51-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Dong, Junmin published the artcileDesign, synthesis and biological evaluation of exiguamine A analogues as IDO1 inhibitors, SDS of cas: 104-01-8, the main research area is exiguamine A preparation SAR mol docking antitumor indoleamine dioxygenase; Cancer immunotherapy; Exiguamine A; Indoleamine 2,3-dioxygenase 1.

A series of exiguamine A analogs were designed and synthesized via 15 steps. Their inhibitory activities against IDO1 were tested and the structure-activity relationships were studied. Most compounds exhibited potent IDO1 inhibitory activities with IC50 values at the level of 10-7-10-8 M. Compound I was the most potent IDO1 inhibitor with an IC50 value of 65.3 nM, which was comparable with the pos. control drug epacadostat (IC50 = 46 nM). Moreover, compound I showed higher selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO) and no cytotoxicity at its effective concentration, rending it justifiable for further optimization and evaluation.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, SDS of cas: 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Liu, Wenjing published the artcileDesign, synthesis and biological evaluation of novel 4-(4-methoxynaphthalen-1-yl)-5-arylpyrimidin-2-amines as tubulin polymerization inhibitors, SDS of cas: 104-01-8, the main research area is methoxynaphthalenylarylpyrimidinamine preparation tubulin polymerization inhibitor antitumor; anticancer; naphthalene; pyrimidine; tubulin polymerization inhibitor.

A novel series of 4-(4-methoxynaphthalen-1-yl)-5-arylpyrimidin-2-amines I (R = 4-OEt, 4-Me, 4-Cl, etc.) were designed, synthesized, and evaluated for their anticancer activities. Most of the synthesized compounds exhibited moderate to high antiproliferative activity in comparison to the standard drug cisplatin. Among them, I (R = 4-OEt) was found to be the most active on MCF-7 and HepG2 cancer cell lines, with IC50 values of 3.77 +/= 0.36 and 3.83 +/= 0.26μM, resp. Further mechanism study shown that I (R = 4-OEt) potently inhibited tubulin polymerization, induced cell cycle arrest at G2/M phase and cell apoptosis in MCF-7 cell line. Furthermore, mol. modeling study suggested that I (R = 4-OEt) probably binds to the colchicine site of tubulin.

Chemical & Pharmaceutical Bulletin published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, SDS of cas: 104-01-8.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Hng, Yue published the artcileDesign and synthesis of 3-benzylaminocoumarin-7-O-sulfamate derivatives as steroid sulfatase inhibitors, Safety of 2,3-Dimethoxybenzaldehyde, the main research area is benzylaminocoumarin sulfamate synthesis anticancer SAR steroid sulfatase breast cancer; Breast cancer; Coumarin; Hormone dependent cancer; Irreversible inhibitors; Steroid sulfatase; Sulfamate.

Steroid sulfatase (STS) is a sulfatase enzyme that catalyzes the conversion of sulfated steroid precursors to free steroid. The inhibition of STS could abate estrogenic steroids that stimulate the proliferation and development of breast cancer, and therefore STS is a potential target for adjuvant endocrine therapy. In this study, a series of 3-benzylaminocoumarin-7-O-sulfamate derivatives targeting STS were designed and synthesized. Structure–activity relationship (SAR) anal. revealed that attachment of a benzylamino group at the 3-position of coumarin improved inhibitory activity. Compound 3j was found to have the highest inhibition activity against human placenta isolated STS (IC50 0.13 μM) and MCF-7 cell lines (IC50 1.35 μM). Kinetic studies found compound 3j to be an irreversible inhibitor of STS, with KI and kinact value of 86.9 nM and 158.7 min-1, resp.

Bioorganic 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, Safety of 2,3-Dimethoxybenzaldehyde.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Shergalis, Andrea published the artcileCharacterization of Aminobenzylphenols as Protein Disulfide Isomerase Inhibitors in Glioblastoma Cell Lines, Quality Control of 86-51-1, the main research area is aminobenzylphenol structure screening preparation PDIA1 inhibitor glioblastoma.

Disulfide bond formation is a critical post-translational modification of newly synthesized polypeptides in the oxidizing environment of the endoplasmic reticulum and is mediated by protein disulfide isomerase (PDIA1). In this study, we report a series of α-aminobenzylphenol analogs as potent PDI inhibitors. The lead compound, AS15, is a covalent nanomolar inhibitor of PDI, and the combination of AS15 analogs with glutathione synthesis inhibitor buthionine sulfoximine (BSO) leads to synergistic cell growth inhibition. Using nascent RNA sequencing, we show that an AS15 analog triggers the unfolded protein response in glioblastoma cells. A BODIPY-labeled analog binds proteins including PDIA1, suggesting that the compounds are cell-permeable and reach the intended target. Taken together, these findings demonstrate an extensive biochem. characterization of a novel series of highly potent reactive small mols. that covalently bind to PDI.

Journal of Medicinal 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, Quality Control of 86-51-1.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Liew, Lydia P. published the artcileHypoxia-Activated Prodrugs of PERK Inhibitors, Formula: C9H10O3, the main research area is hypoxia prodrug drug delivery PERK kinase inhibitor antitumor; drug delivery; hypoxia; kinase inhibitor; nitroimidazole; prodrug.

Tumor hypoxia plays an important role in tumor progression and resistance to therapy. Under hypoxia unfolded proteins accumulate in the endoplasmic reticulum (ER) and this stress is relieved through the protein kinase R-like ER kinase (PERK) signaling arm of the unfolded protein response (UPR). Targeting the UPR through PERK kinase inhibitors provides tumor growth inhibition, but also elicits on-mechanism normal tissue toxicity. Hypoxia presents a target for tumor-selective drug delivery using hypoxia-activated prodrugs. We designed and prepared hypoxia-activated prodrugs of modified PERK inhibitors using a 2-nitroimidazole bioreductive trigger. The new inhibitors retained PERK kinase inhibitory activity and the corresponding prodrugs were strongly deactivated. The prodrugs were able to undergo fragmentation following radiolytic reduction, or bioreduction in HCT116 cells, to release their effectors, albeit inefficiently. We examined the effects of the prodrugs on PERK signaling in hypoxic HCT116 cells. This study has identified a 2-substituted nitroimidazole carbamate prodrug with potential to deliver PERK inhibitors in a hypoxia-selective manner.

Chemistry – An Asian Journal published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Formula: C9H10O3.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Zheng, Di-Wei published the artcileHighly Integrated Nano-Platform for Breaking the Barrier between Chemotherapy and Immunotherapy, Category: isoquinoline, the main research area is nanoparticle chemotherapy immunotherapy breast cancer metastasis; Theranostic platform; imaging; immune response; target; tumor therapy.

Fighting metastasis is a major challenge in cancer therapy, and stimulation of the immune system is of particular importance in the treatment of metastatic cancers. Here, an integrated theranostic nanoplatform was developed for the efficient treatment of highly metastatic tumors. Versatile functions including “”And”” logically controlled drug release, prolonged circulation time, tumor targeting, and anti-metastasis were integrated into doxorubicin (DOX) loaded, highly integrated mesoporous silica nanoparticles (DOX@HIMSNs) for a systemic treatment of highly metastatic triple neg. breast cancer (TNBC). It was found that the good therapeutic effect of DOX@HIMSN was only partially attributed to its anticancer cytotoxicity. Most importantly, DOX@HIMSN could induce anticancer immune responses including dendritic cell (DC) maturation and antitumor cytokine release. Compared with the traditional tumor chemotherapy, the integrated theranostic nanoplatform we developed not only improved the tumor specific cytotoxicity but also stimulated antitumor immune responses during the treatment.

Nano Letters published new progress about Antitumor agents. 117-96-4 belongs to class isoquinoline, name is Diatrizoic Acid, and the molecular formula is C11H9I3N2O4, Category: isoquinoline.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Choodamani, B. published the artcileSynthesis, Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole, Name: 4-Methoxyphenylacetic acid, the main research area is methoxybenzyl derivative mol docking antitimor agent; TGF beta receptor kinase; cytotoxicity; imidazothiadiazole; levamisole; melphalan.

In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1-b][1,3,4]thiadiazole. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identified two compounds, 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate and 6-(4-chlorophenyl)-2-(4-methoxybenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde, exhibited the most cytotoxic effect against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC50 values ranging between 0.79 and 1.6μM. The results indicate that 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate is inducing phosphatidylserine externalization and caspase-3 activation which are both a hallmark of apoptosis. Docking studies showed that 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate binds within the active sites of transforming growth factor beta (TGF-β) type I receptor kinase domain by strong hydrogen binding and hydrophobic interactions.

Chemistry & Biodiversity published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Name: 4-Methoxyphenylacetic acid.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem

Farand, Julie published the artcileDiscovery of Potent and Selective MTH1 Inhibitors for Oncology: Enabling Rapid Target (In)Validation, Synthetic Route of 598-50-5, the main research area is antitumor drug target MTH1 inhibitor preparation tetrahydro naphthyridine derivative.

We describe the discovery of three structurally differentiated potent and selective MTH1 inhibitors and their subsequent use to investigate MTH1 as an oncol. target, culminating in target (in)validation. Tetrahydronaphthyridine 5 was rapidly identified as a highly potent MTH1 inhibitor (IC50 = 0.043 nM). Cocrystn. of 5 with MTH1 revealed the ligand in a Φ-cis-N-(pyridin-2-yl)acetamide conformation enabling a key intramol. hydrogen bond and polar interactions with residues Gly34 and Asp120. Modification of literature compound TH287 with O- and N-linked aryl and alkyl aryl substituents led to the discovery of potent pyrimidine-2,4,6-triamine 25 (IC50 = 0.49 nM). Triazolopyridine 32 emerged as a highly selective lead compound with a suitable in vitro profile and desirable pharmacokinetic properties in rat. Elucidation of the DNA damage response, cell viability, and intracellular concentrations of oxo-NTPs (oxidized nucleoside triphosphates) as a function of MTH1 knockdown and/or small mol. inhibition was studied. Based on our findings, we were unable to provide evidence to further pursue MTH1 as an oncol. target.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 598-50-5 belongs to class isoquinoline, name is 1-Methylurea, and the molecular formula is C2H6N2O, Synthetic Route of 598-50-5.

Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem