Browse
Submit Data
Databases
API
Help

Dataset Information

36 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of Some Spiro Indeno[1,2-b]pyrido[2,3-d]Pyrimidine-5,3'-Indolines as New Urease Inhibitors.

ABSTRACT: New series of spiro indeno[1,2-b]pyrido[2,3-d]pyrimidine-5,3'-indolines as new urease inhibitors were synthesized by the catalytic procedure in high yield and short reaction time. In this method, biacidic carbon was prepared as a novel heterogeneous acid and was subsequently used as an efficient catalyst. The inhibitory activities of synthesized compounds were tested against Jack bean urease using Berthelot colorimetric assay and docking simulation using AutoDock 4.2. The compound 4a with IC50 =1.94 µM has the most inhibitor activity in this study. Other derivatives such as 4b, 4d, 4e and 7a were found to be more potent urease inhibitors than the standard inhibitor hydroxyurea, yielding IC50 values of 4.35, 5.557, 7.44, 2.81 and 14.46 ?M, respectively (IC50 of hydroxyurea = 100 ?M).

SUBMITTER: Mohammadi Ziarani G

PROVIDER: S-EPMC5242352 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of Some Spiro Indeno[1,2-b]pyrido[2,3-d]Pyrimidine-5,3'-Indolines as New Urease Inhibitors.

Mohammadi Ziarani Ghodsi G Asadi Shima S Badiei Alireza A Sharifi Amirhossein A Amanlou Massoud M

Iranian journal of pharmaceutical research : IJPR 20160101 Suppl

New series of spiro indeno[1,2-b]pyrido[2,3-d]pyrimidine-5,3'-indolines as new urease inhibitors were synthesized by the catalytic procedure in high yield and short reaction time. In this method, biacidic carbon was prepared as a novel heterogeneous acid and was subsequently used as an efficient catalyst. The inhibitory activities of synthesized compounds were tested against Jack bean urease using Berthelot colorimetric assay and docking simulation using AutoDock 4.2. The compound ...[more]

PMID: 28228804

Similar Datasets

Synthesis and anticancer evaluation of diaryl pyrido[2,3-d]pyrimidine /alkyl substituted pyrido[2,3-d]pyrimidine derivatives as thymidylate synthase inhibitors.

Project description:Worldwide, colorectal cancer (CRC) is the third most common type of cancer and the second most common cause of cancer-related deaths. Thymidylate synthase (TS) is a crucial component of DNA biosynthesis and has drawn interest as an essential target for cancer treatment. In the current work, we have designed and synthesized twenty-eight new diaryl-based pyrido[2,3-d]pyrimidine/alkyl-substituted pyrido[2,3-d]pyrimidine derivatives and evaluated their anticancer activity against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines cell lines. Additionally, we have carried out TS inhibitory activity and in silico studies for compounds 1n and 2j. All the synthesized compounds exhibited good anticancer activity, but among them, compounds 1n and 2j showed excellent anticancer activity, having IC50 values of 1.98 ± 0.69, 2.18 ± 0.93, 4.04 ± 1.06, and 4.18 ± 1.87 µM; and 1.48 ± 0.86, 3.18 ± 0.79, 3.44 ± 1.51, and 5.18 ± 1.85 µM, against the HCT 116, MCF-7, Hep G2, and PC-3 cell lines respectively with control raltitrexed (IC50 1.07 ± 1.08, 1.98 ± 0.72, 1.34 ± 1.0, and 3.09 ± 0.96 µM, respectively) and hTS inhibitory activity with IC50 values of 20.47 ± 1.09 and 13.48 ± 0.96 nM with control raltitrexed (IC50 14.95 ± 1.01 nM). Further, the mechanism of inhibition was revealed by molecular docking, which showed the binding pattern of 1n and 2j to the catalytic site of TS with docking scores of -10.6 and - 9.5 kcal/mol, respectively, with reference raltitrexed (-9.4 kcal/mol). Additionally, the assessment of physicochemical, biochemical, structural, and toxicological characteristics were also in the acceptable range for these compounds. Based on the anticancer activity of compounds, SAR was also performed for lead optimization.

| S-EPMC11361161 | biostudies-literature

Spiro-[cyclo-pentane-1,2'(1'H)-pyrido[2,3-d]pyrimidin]-4'(3'H)-one.

Project description:The title compound, C(11)H(13)N(2)O, was obtained by cyclo-condensation of 2-amino-pyridine-3-carbonitrile with cyclo-penta-none. The mol-ecule is built up from two fused six-membered rings and one five-membered ring linked through a spiro C atom. Both the pyrimidine and the cyclo-pentane rings adopt envelope conformations. In the crystal structure, mol-ecules are linked by inter-molecular N-H⋯O hydrogen bonds.

| S-EPMC3008029 | biostudies-literature

6'-Bromo-1'H-spiro-[cyclo-hexane-1,2'-pyrido[2,3-d]pyrimidin]-4'(3'H)-one.

Project description:The title compound, C(12)H(14)BrN(3)O, is built up from two fused six-membered rings and one six-membered ring linked through a spiro C atom. The hydro-pyrimidine ring has an envelope conformation and the cyclo-hexane ring is in a chair conformation. In the crystal, mol-ecules are linked by N-H?O and N-H?N hydrogen bonds, forming a mol-ecular tape along the b axis.

| S-EPMC3254517 | biostudies-literature

6'-Amino-3'-methyl-11H,2'H-spiro-[indeno-[1,2-b]quinoxaline-11,4'-pyrano[2,3-c]pyrazole]-5'-carbonitrile ethanol monosolvate.

Project description:In the title spiro-indeno-quinoxaline compound, C(22)H(14)N(6)O·C(2)H(6)O, the five-membered ring of the indene unit and the pyran ring are perpendicular [89.11 (3)°]. In the crystal, N-H⋯N hydrogen bonds connect the spiro-indeno-quinoxaline mol-ecules, and the ethanol solvent mol-ecules complete the hydrogen-bond network via O-H⋯N and N-H⋯O inter-actions.

| S-EPMC3393959 | biostudies-literature

Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors.

Project description:A small molecule library of pyrido[2,3-d]pyrimidine-2,4-dione derivatives 6-16 was synthesized from 6-amino-1,3-disubstituted uracils 18, characterized, and screened for inhibitory activity against eukaryotic elongation factor-2 kinase (eEF-2K). To understand the binding pocket of eEF-2K, structural modifications of the pyrido[2,3-d]pyrimidine were made at three regions (R(1), R(2), and R(3)). A homology model of eEF-2K was created, and compound 6 (A-484954, Abbott laboratories) was docked in the catalytic domain of eEF-2K. Compounds 6 (IC50=420nM) and 9 (IC50=930nM) are found to be better molecules in this preliminary series of pyrido[2,3-d]pyrimidine analogs. eEF-2K activity in MDA-MB-231 breast cancer cells is significantly reduced by compound 6, to a lesser extent by compound 9, and is unaffected by compound 12. Similar inhibitory results are observed when eEF-2K activity is stimulated by 2-deoxy-d-glucose (2-DOG) treatment, suggesting that compounds 6 and 9 are able to inhibit AMPK-mediated activation of eEF-2K to a notable extent. The results of this work will shed light on the further design and optimization of novel pyrido[2,3-d]pyrimidine analogs as eEF-2K inhibitors.

| S-EPMC6473179 | biostudies-literature

Anticancer evaluation and molecular modeling of multi-targeted kinase inhibitors based pyrido[2,3-d]pyrimidine scaffold.

Project description:An efficient synthesis of substituted pyrido[2,3-d]pyrimidines was carried out and evaluated for in vitro anticancer activity against five cancer cell lines, namely hepatic cancer (HepG-2), prostate cancer (PC-3), colon cancer (HCT-116), breast cancer (MCF-7), and lung cancer (A-549) cell lines. Regarding HepG-2, PC-3, HCT-116 cancer cell lines, 7-(4-chlorophenyl)-2-(3-methyl-5-oxo-2,3-dihydro-1H-pyrazol-1-yl)-5-(p-tolyl)- pyrido[2,3-d]pyrimidin-4(3H)-one (5a) exhibited strong, more potent anticancer (IC50: 0.3, 6.6 and 7 µM) relative to the standard doxorubicin (IC50: 0.6, 6.8 and 12.8 µM), respectively. Kinase inhibitory assessment of 5a showed promising inhibitory activity against three kinases namely PDGFR β, EGFR, and CDK4/cyclin D1 at two concentrations 50 and 100 µM in single measurements. Further, a molecular docking study for compound 5a was performed to verify the binding mode towards the EGFR and CDK4/cyclin D1 kinases.

| S-EPMC6009920 | biostudies-literature

6-Ferrocenoyl-7-phenyl-spiro-[hexa-hydro-pyrrolo-[1,2-c][1,3]thia-zole-5,11'-indeno-[1,2-b]quinoxaline].

Project description:In the title compound, [Fe(C5H5)(C32H24N3OS)], both the thia-zolidine ring and the pyrrolidine ring adopt an envelope conformation, with the S atom and the phenyl-bearing C atom, respectively, as the flaps. The thia-zolidine ring mean plane makes a dihedral angle of 59.08?(11)° with the pyrrolidine ring mean plane, which in turn makes a dihedral angle of 83.40?(10)° with the cyclo-pentane ring, indicating that the latter two rings are almost orthogonal to one another. In the crystal, a pair of C-H?O hydrogen bonds link the mol-ecules forming inversion dimers. The dimers are linked via ?-? inter-actions [centroid-centroid distance = 3.7764?(10)?Å] involving the quinoxaline moieties forming chains propagating along [1-10].

| S-EPMC3884422 | biostudies-literature

2-(4-Bromo-benzo-yl)-1-ferrocenyl-spiro-[11H-pyrrolidizine-3,11'-indeno-[1,2-b]quinoxaline].

Project description:In the title compound, [Fe(C5H5)(C33H25BrN3O)], the fused four-ring system, 11H-indeno-[1,2-b]quinoxaline is essentially planar, with a maximum deviation of 0.087?(3)?Å from the least-squares plane of the attached benzene ring. The pyrrolidine rings adopt envelope conformation and make a dihedral angle of 51.76?(19)° with each other. The cyclopentadiene rings of the ferrocenyl moiety have an eclipsed conformation. The Br atom deviates by 0.0190?(9)?Å from the attached benzene ring. The mol-ecular structure features an intra-molecular C-H?N inter-action, which generates an S(8) ring motif. The crystal packing features C-H?O inter-actions, which generate R 2 (2)(18) centrosymmetric dimers, as well as C-H?? inter-actions.

| S-EPMC3884418 | biostudies-literature

Synthesis of novel bioactive pyrido[2,3-d]pyrimidine derivatives with potent cytotoxicity through apoptosis as PIM-1 kinase inhibitors.

Project description:Direct synthesis and cytotoxicity activity of new series of pyrido[2,3-d]pyrimidine was described. Nicotinamide 2 was synthesized via cyclization of N-cyclohexyl derivative with cyanoacetamide. The o-aminonicotinonitrile 2 was subjected to acylation or thio acylation process followed by intramolecular heterocyclization to afford the desired pyrido[2,3-d]pyrimidine (3-10) and pyrido triazine 11. Compounds 4 and 11 exhibited remarkable cytotoxicity against MCF-7 cells with IC50 values of 0.57 μM and 1.31 μM and IC50 values of 1.13 μM and 0.99 μM against HepG2 cells. Interestingly, compounds 4 and 10 had potent PIM-1 kinase inhibition with IC50 values of 11.4 and 17.2 nM, respectively, with inhibition of 97.8% and 94.6% compared to staurosporine (IC50 = 16.7 nM, with 95.6% inhibition). Moreover, compound 4 significantly activated apoptosis in MCF-7 cells, increasing the cell apoptosis by 58.29-fold by having 36.14% total apoptosis in treated cells compared to 0.62% for control. Moreover, it arrested the cell cycle at the G1 phase. PIM-1 kinase inhibition was virtually elucidated by the molecular docking study, highlighting binding interactions of the lead compound 4 towards the PIM-1 protein. Accordingly, compound 4 was validated as a promising PIM-1 targeted chemotherapeutic agent to treat breast cancer.

| S-EPMC10996840 | biostudies-literature

6-Ferrocenoyl-7-(4-fluoro-phen-yl)spiro-[hexa-hydro-pyrrolo-[1,2-c][1,3]thia-zole-5,11'-indeno-[1,2-b]quinoxaline].

Project description:In the title compound, [Fe(C5H5)(C32H23FN3OS)], both the thia-zolidine ring and the pyrrolidine ring adopt a twist conformation on the N-C(H) bridging bond. Their mean planes are inclined to one another by 10.05?(10)°, and they make dihedral angles of 82.09?(10) and 89.67?(11)°, respectively, with the cyclo-pentane ring. The F atom deviates by -0.0238?(2)?Å from the benzene ring to which it is attached. In the crystal, mol-ecules are linked by a pair of C-H?O hydrogen bonds, forming inversion dimers.

| S-EPMC3884446 | biostudies-literature