67929-86-6Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole analogs as melatonin receptor ligands
Attia, Mohamed I.,Julius, Justin,Witt-Enderby, Paula A.,Zlotos, Darius P.
, p. 754 - 760 (2007)
The synthesis of two melatonin-derived analogs of the novel 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole ring system is described. The non-methoxy and methoxy analogs, 4a and 4b were prepared in seven steps starting from indoline-2-carboxylic acid 5a and 5-methoxyindoline-2-carboxylic acid 5b, respectively. While 4a exhibited micromolar affinities for both melatonin receptors, the methoxy analog 4b displayed moderate affinity for MT2 receptors (Ki=0.41 μM) being 4.4-fold higher than for the MT1 subtype.
Design and synthesis of two cytotoxic analogs of the novel pyrrolo[1′,2′:1,2][1,4]diazepin [7,6-b]indol-5(6h)-one nucleus
Tsotinis, Andrew,Vlachou, Margarita,Kiakos, Konstantinos,Hartley, John A.,Thurston, David E.
, p. 512 - 513 (2003)
The design and synthesis of the two cytotoxic derivatives 15 and 16 of the novel pyrrolo[1′,2′:1,2][1,4]diazepin[7,6-b]indol-5(6H)-one nucleus is described. Readily available methyl 2-indolecarboxylates 5 and 6 are nitrosated with NaNO2 in AcOH to give the analogs 7 and 8, which are then oxidized with KMnO4 in aq. NaOH to provide the 3-NO2 acids 9 and 10. These, in turn, are subjected to amidation with (2S)-pyrrolidine-2-carboxaldehyde diethyl thioacetal in the presence of EDCI and HOBt and then to a 7-exo-trig cyclization reaction to give the target molecules 15 and 16. The new analogs were evaluated in the human leukemic K 562 cell line and were shown to have micromolar potency.
Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and computational studies on methyl 5-methoxy-1H-indole-2-carboxylate: A potential precursor to biologically active molecules
Almutairi, Maha S.,Xavier,Sathish,Ghabbour, Hazem A.,Sebastian,Periandy,Al-Wabli, Reem I.,Attia, Mohamed I.
, p. 199 - 210 (2017)
Methyl 5-methoxy-1H-indole-2-carboxylate (MMIC) was prepared via esterification of commercially available 5-methoxyindole-2-carboxylic acid. The title molecule MMIC was characterised using FT-IR and FT-Raman in the ranges of 4000–500 and 4000–50?cm?1, respectively. The fundamental modes of the vibrations were assigned and the UV–visible spectrum of the MMIC molecule was recorded in the range of 200–400?nm to explore its electronic nature. The HOMO-LUMO energy distribution was calculated and the bonding and anti-bonding structures of the title molecule were studied and analysed using the natural bond orbital (NBO) approach. The reactivity of the MMIC molecule was also investigated and both the positive and negative centres of the molecule were identified using chemical descriptors and molecular electrostatic potential (MEP) analysis. The chemical shifts of the 1H and 13C NMR spectra were noted and the magnetic field environment of the MMIC molecule are discussed. The non-linear optical (NLO) properties of the title molecule were studied based on its calculated values of polarisability and hyperpolarisability. All computations were obtained by DFT methods using the 6-311++G (d,p) basis set.
Iodine/Manganese Catalyzed Sulfenylation of Indole via Dehydrogenative Oxidative Coupling in Anisole
Li, Weihe,Wang, Hao,Liu, Shengping,Feng, Hua,Benassi, Enrico,Qian, Bo
supporting information, p. 2666 - 2671 (2020/05/25)
This protocol describes an iodine/manganese catalytic system for dehydrogenative oxidative coupling reaction of indoles with thiols in anisole. Particularly, the dual roles of anisole have been first demonstrated as a solvent and as a promoter via the formation of an oxonium ion intermediate to accelerate the generation of products. A series of sulfenylindoles are readily constructed under aerobic mild reaction conditions. In addition, the achievement for preparing anticancer and anti-AIDS drugs testifies the practicability of this approach. The mechanism studies disclose probable alternative pathways and a single-electron transfer process are involved in this transformation. (Figure presented.).
Novel indole hydrazide derivatives: Synthesis and their antiproliferative activities through inducing apoptosis and DNA damage
Kilic-Kurt, Zühal,Acar, Cemre,Ergul, Mustafa,Bakar-Ates, Filiz,Altuntas, Tunca G.
, (2020/05/21)
A series of novel indole hydrazide derivatives was synthesized and evaluated for their anticancer activities. Compound 12 exhibited the highest antiproliferative activity against the MCF-7 cell line, with an IC50 value of 3.01 μM. Treatment of MCF-7 cells with compound 12 led to cell cycle arrest at the G0/G1 phase and also displayed a significant annexin V binding pattern, indicating that compound 12 is effective in apoptotic cell death. The Western blot analysis showed that compound 12 increased the expression of proapoptotic Bax and decreased the levels of the antiapoptotic Bcl-2 protein. It was also observed that MCF-7 cells treated with compound 12 showed reduced levels of procaspase-3 and -9 proteins. Moreover, compound 12 treatment induced a significant DNA damage in MCF-7 cells by increasing H2AX and ATM phosphorylation.
Antiproliferative activity and possible mechanism of action of certain 5-methoxyindole tethered C-5 functionalized isatins
Almutairi, Maha S.,Hassan, Eman S.,Keeton, Adam B.,Piazza, Gary A.,Abdelhameed, Ali S.,Attia, Mohamed I.
, p. 3069 - 3078 (2019/09/10)
Background: Cancer is one of the most dreaded human diseases, that has become an ever-increasing health problem and is a prime cause of death globally. The potential antiproliferative activity of certain indole–isatin molecular hybrids 5a-w was evaluated in vitro against three human cancer cell lines. Methods: Standard protocols were adopted to examine the antiproliferative potential and mechanisms of compounds 5a-w. Western blot analysis was carried out on compound 5o. Results: Compounds 5a-w demonstrated in vitro antiproliferative activity in the range of 22.6–97.8%, with compounds 5o and 5w being the most active antiproliferative compounds with IC50 values of 1.69 and 1.91 μM, which is fivefold and fourfold more potent than sunitinib (IC50=8.11 μM), respectively. Compound 5o was selected for in-depth pharmacological testing to understand its possible mechanism of antiproliferative activity. It caused a lengthening of the G1 phase and a reduction in the S and G2/M phases of the cell cycle and had an IC50 value of 10.4 μM with the resistant NCI-H69AR cancer cell line. Moreover, compound 5o significantly decreased the amount of phosphorylated Rb protein in a dose-dependent fashion, which was confirmed via Western blot analysis. Conclusion: The current investigation highlighted the potential antiproliferative activity of compounds 5a-w as well as the antiproliferative profile of compound 5o. These compounds can be harnessed as new lead antiproliferatives in the preclinical studies of cancer chemotherapy.
Palladium(0)-Catalyzed Intermolecular Asymmetric Cascade Dearomatization Reaction of Indoles with Propargyl Carbonate
Ding, Lu,Gao, Run-Duo,You, Shu-Li
supporting information, p. 4330 - 4334 (2019/02/25)
An intermolecular asymmetric cascade dearomatization reaction of indole derivatives with propargyl carbonate was developed. The challenges associated with both the chemoselectivity between the carbon and nitrogen nucleophile and the enantioselective control during the formation of an all-carbon quaternary stereogenic center were well addressed by a Pd catalytic system derived from the Feringa ligand. A series of enantioenriched multiply substituted fused indolenines were provided in good yields (71–86 %) with excellent enantioselectivity (91–96 % ee) and chemoselectivity (3/4>19:1 in most cases).
Synthesis, spectroscopic identification and molecular docking of certain N-(2-[2-(1H-Indol-2-ylcarbonyl) hydrazinyl](oxo)acetyl phenyl)acetamides and N-[2-(2-[2-(Acetylamino)phenyl](oxo)acetyl hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides: New antimicrobial agents
Almutairi, Maha S.,Zakaria, Azza S.,Al-Wabli, Reem I.,Hubert Joe,Abdelhameed, Ali S.,Attia, Mohamed I.
, (2018/05/22)
N-(2-[2-(1H-Indol-2-ylcarbonyl)hydrazinyl](oxo)acetyl phenyl)acetamides (5a–h) and N-[2-(2-[2-(acetylamino)phenyl](oxo)acetyl hydrazinyl)-2-oxoethyl]-1H-indole-2-carboxamides (5i–l) were synthesized and characterized with different analytical tools. N-Acetylisatines 4a–d were subjected to ring opening at their C2 carbons with the aid of different indole-bearing hydrazides 3a,b and 7 to afford the respective glyoxylamides 5a–l. The antimicrobial activity of the target compounds 5a–l was assessed with the aid of Diameter of the Inhibition Zone (DIZ) and Minimum Inhibitory Concentration (MIC) assays against a panel of Gram-positive and Gram-negative bacteria and certain fungal strains. The antimicrobial screening revealed that Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans are the most sensitive microorganisms towards the synthesized compounds 5a–l. In addition, compounds 5c and 5h emerged as the most active congeners towards Staphylococcus aureus and Candida albicans, respectively. Molecular docking studies revealed the possible binding mode of compounds 5c and 5h to their target proteins.
Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches
Almutairi, Maha S.,Zakaria, Azza S.,Ignasius, P. Primsa,Al-Wabli, Reem I.,Joe, Isaac Hubert,Attia, Mohamed I.
, p. 333 - 345 (2017/10/18)
Indole-isatin molecular hybrids 5a-i have been synthesized and characterized by different spectroscopic methods to be evaluated as new antimicrobial agents against a panel of Gram positive bacteria, Gram negative bacteria, and moulds. Compound 5h was selected as a representative example of the prepared compounds 5a-i to perform computational investigations. Its vibrational properties have been studied using FT-IR and FT-Raman with the aid of density functional theory approach. The natural bond orbital analysis as well as HOMO and LUMO molecular orbitals investigations of compound 5h were carried out to explore its possible intermolecular delocalization or hyperconjugation and its possible interactions with the target protein. Molecular docking of compound 5h predicted its binding mode with the fungal target protein.
PYRROLOBENZODIAZEPINE PRODRUGS AND ANTIBODY CONJUGATES THEREOF
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Page/Page column 180; 181; 184, (2018/03/06)
The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.
