Regioselective synthesis and theoretical studies of an anti-neoplastic fluoro-substituted dispiro-oxindole

Girgis, Adel S.; Panda, Siva S.; Shalaby, ElSayed M.; Mabied, Ahmed F.; Steel, Peter J.; Hall, C. Dennis; Katritzky, Alan R.

doi:10.1039/c4ra13433h

Cited by 25 publications

(26 citation statements)

References 44 publications

(40 reference statements)

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“…The four substituents of the central dihydrofuran ring are arranged in an all-trans configuration, thus avoiding steric hindrance between the aryl groups. The bond lengths (Allen et al, 1987) and angles in all four structures are in agreement with similar structures reported in the literature (Ravikumar et al, 2015b;Girgis et al, 2015). The dihydrofuran ring adopts an envelope conformation, with atom O2 as the flap in (I), (II), (III) (molecule A) and (IV) (molecule B), while it is twisted on the C9-O2 bond in (III) (molecule B) and (IV) (molecule A).…”

Section: Resultssupporting

confidence: 88%

Structural consequences of weak interactions in dispirooxindole derivatives

et al. 2015

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Spiro scaffolds are being increasingly utilized in drug discovery due to their inherent three-dimensionality and structural variations, resulting in new synthetic routes to introduce spiro building blocks into more pharmaceutically active molecules. Multicomponent cascade reactions, involving the in situ generation of carbonyl ylides from α-diazocarbonyl compounds and aldehydes, and 1,3-dipolar cycloadditon with 3-arylideneoxindoles gave a novel class of dispirooxindole derivatives, namely 1,1''-dibenzyl-5'-(4-chlorophenyl)-4'-phenyl-4',5'-dihydrodispiro[indoline-3,2'-furan-3',3''-indoline]-2,2''-dione, C44H33ClN2O3, (I), 1''-acetyl-1-benzyl-5'-(4-chlorophenyl)-4'-phenyl-4',5'-dihydrodispiro[indoline-3,2'-furan-3',3''-indoline]-2,2''-dione, C39H29ClN2O4, (II), 1''-acetyl-1-benzyl-4',5'-diphenyl-4',5'-dihydrodispiro[indoline-3,2'-furan-3',3''-indoline]-2,2''-dione, C39H30N2O4, (III), and 1''-acetyl-1-benzyl-4',5'-diphenyl-4',5'-dihydrodispiro[indoline-3,2'-furan-3',3''-indoline]-2,2''-dione acetonitrile hemisolvate, C39H30N2O4·0.5C2H3N, (IV). All four compounds exist as racemic mixtures of the SSSR and RRRS stereoisomers. In these structures, the two H atoms of the dihydrofuran ring and the two substituted oxindole rings are in a trans orientation, facilitating intramolecular C-H···O and π-π interactions. These weak interactions play a prominent role in the structural stability and aid the highly regio- and diastereoselective synthesis. In each of the four structures, the molecular assembly in the crystal is also governed by weak noncovalent interactions. Compound (IV) is the solvated analogue of (III) and the two compounds show similar structural features.

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Section: Resultssupporting

confidence: 88%

Structural consequences of weak interactions in dispirooxindole derivatives

et al. 2015

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“…The RHF (Restricted Hartree-Fock) method was used in spin pairing for the two semi-empirical tools. [28][29][30][31][32]38,39 The resulting output files were exported to CODESSA-Pro that includes MOPAC capability for the final geometry optimization.…”

Section: Methodsmentioning

confidence: 99%

“…The synthesized peptidomimetics 4a-4l, and 5-7 were also bio-assayed against five human cancer cell lines: HeLa (cervical), PC-3 (prostate), MCF-7 (breast), HepG2 (liver) and HCT-116 (colon) utilizing the standard in-vitro Sulfo-Rhodamine-B (SRB) method, [29][30][31][32][33][34][35][36][37] in order to evaluate the antiproliferative potential. Table 4 illustrates that almost all the peptidomimetics have low cytotoxic activity against human cell lines, with only 4a (against HepG2 with IC 50 = 6.03 μM, IC 50 of doxorubicin = 7.36 μM) and 4l (against PC3 with IC 50 = 7.94 μM, IC 50 of doxorubicin = 8.83 μM) being as active as the reference standard doxorubicin.…”

Section: Antitumor Bioassaymentioning

confidence: 99%

“…[28][29][30][31][32][33][34][35][36] Cells were seeded in 96-well microtiter plates at a concentration of 5 x 10 4 -10 5 cell/well in a fresh medium and left for 24 h before treatment with the tested compounds to allow attachment of cells to the wall of the plate. The tested compounds were dissolved in DMSO and diluted 1000-fold in the assay.…”

Section: Antitumor Activity Screeningmentioning

confidence: 99%

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Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies

et al. 2015

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Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

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“…The RHF (Restricted Hartree-Fock) method was used in spin pairing for the semi-empirical tools. [32][33][34][35][36][37][38][39][40][41] The resulting output files were exported to CODESSA-Pro that include MOPAC capability for final geometry optimization. CODESSA-Pro calculated 632 molecular descriptors including constitutional, topological, geometrical, charge-related, semi-empirical, molecular-type, atomic-type and bond-type descriptors for the exported 26 antibacterial active compounds (S1-S4, 10a-f, 11a-f, 13a-f and 14a-f).…”

Section: Introductionmentioning

confidence: 99%

Novel antibacterial active quinolone–fluoroquinolone conjugates and 2D-QSAR studies

Panda

Liaqat

Girgis

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Regioselective synthesis and theoretical studies of an anti-neoplastic fluoro-substituted dispiro-oxindole

Abstract: An anti-neoplastic fluoro-substituted dispiro-oxindole is described along with theoretical studies and single crystal X-ray analysis.

Cited by 25 publications

References 44 publications

Structural consequences of weak interactions in dispirooxindole derivatives

Structural consequences of weak interactions in dispirooxindole derivatives

Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies

Novel antibacterial active quinolone–fluoroquinolone conjugates and 2D-QSAR studies

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