10511-51-0Relevant articles and documents
Novel [(3-indolylmethylene)hydrazono]indolin-2-ones as apoptotic anti-proliferative agents: design, synthesis and in vitro biological evaluation
Eldehna, Wagdy M.,Abo-Ashour, Mahmoud F.,Ibrahim, Hany S.,Al-Ansary, Ghada H.,Ghabbour, Hazem A.,Elaasser, Mahmoud M.,Ahmed, Hanaa Y. A.,Safwat, Nesreen A.
, p. 686 - 700 (2018)
On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a–r, 9a–f and 11a–c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50=1.04 μM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay. Also, 6n increased the expression of caspase-3, caspase-9, cytochrome C and Bax and decreased the expression of Bcl-2. Moreover, compounds 6i, 6j, 6n and 6q generated ROS by significant increase in the level of SOD and depletion of the levels of CAT and GSH-Px in MCF-7.
Synthesis, characterization, and biological evaluation of indole aldehydes containing N-benzyl moiety
Survase, Dattatray N.,Karhale, Shrikrishna S.,Khedkar, Vijay M.,Helavi, Vasant B.
, p. 3486 - 3497 (2019)
The present study describes the synthesis, characterization and biological evaluation of N-benzyl indole aldehydes. The biological activities of the newly synthesized compounds were examined by investigating their antioxidant and anti-inflammatory activities. The potential of these compounds as an antioxidant was determined by 2,2-diphenylpicrylhydrazyl, Nitric oxide, Superoxide, peroxide radical scavenging methods. We found that aldehydes 4a, 4b, 4c, and 4e and shows promising in vitro DPPH scavenging antioxidant activity while aldehyde 4b and 4e show good in vitro anti-inflammatory activity.
Synthesis, crystal structures, and spectral properties of double N-alkylated dimethine cyanine dyes and their interactions with biomolecules and living cells
Jia, Hongliang,Lv, Ying,Wang, Shu,Sun, Dan,Wang, Lanying
, p. 4681 - 4692 (2015)
Six new double N-alkylated dimethine cyanine dyes were synthesized and the crystal structures of two of the dyes were analyzed by X-ray diffraction. The investigation of the spectral properties of the dyes in different solvents indicated that the absorption maxima of the dyes decreased with the increase of the basicity of the heterocyclic nucleus, and the increase of the solvent dielectric constants of the protonic solvents and non-protonic solvents. The six dyes all emitted fluorescence, and had a larger Stokes shift in water. The interaction between the dye molecules and the six biological molecules showed that one dye exhibited a larger enhancement of fluorescent quantum yield in the presence of DNA. Investigation of the cytotoxicity and cell staining of the selected dye showed that the dye had virtually no toxicity at the application dose and duration used and that it could stain cytoplasm, suggesting its potential application as a fluorescent reagent with which to observe and analyze the characteristics of living cells.
Novel indole-thiazolidinone conjugates: Design, synthesis and whole-cell phenotypic evaluation as a novel class of antimicrobial agents
Abo-Ashour, Mahmoud F.,Eldehna, Wagdy M.,George, Riham F.,Abdel-Aziz, Marwa M.,Elaasser, Mahmoud M.,Abdel Gawad, Nagwa M.,Gupta, Antima,Bhakta, Sanjib,Abou-Seri, Sahar M.
, p. 49 - 60 (2018)
In connection with our research program on the development of novel anti-tubercular candidates, herein we report the design and synthesis of two different sets of indole-thiazolidinone conjugates (8a,b; 11a-d) and (14a-k; 15a-h). The target compounds were evaluated for their in vitro antibacterial and antifungal activities against selected human pathogens viz. Staphylococcus aureus (Gram positiveve), Pseudomonas aeruginosa, Escherichia coli (Gram negative), Mycobacterium tuberculosis (Acid-fast bacteria), Aspergillus fumigates and Candida albicans (fungi). Moreover, eukaryotic cell-toxicity was tested via an integrated ex vivo drug screening model in order to evaluate the selective therapeutic index (SI) towards antimicrobial activity when microbes are growing inside primary immune cells. Also, the cytotoxicity towards a panel of cancer cell lines and human lung fibroblast normal cell line, WI-38 cells, was explored to assure their safety. Compound 15b emerged as a hit in this study with potent broad spectrum antibacterial (MIC: 0.39–0.98 μg/mL) and antifungal (MIC: 0.49–0.98 μg/mL) activities, in addition to its ability to kill mycobacteria M. aurum inside an infected macrophage model with good therapeutic window. Moreover, compound 15b displayed promising activity towards resistant bacteria strains MRSA and VRE with MIC values equal 3.90 and 7.81 μg/mL, respectively. These results suggest compound 15b as a new therapeutic lead with good selectivity for further optimization and development.
Iron-Catalyzed C3-Formylation of Indoles with Formaldehyde and Aqueous Ammonia under Air
Wang, Qing-Dong,Zhou, Bin,Yang, Jin-Ming,Fang, Dong,Ren, Jiangmeng,Zeng, Bu-Bing
, p. 2670 - 2674 (2017)
An efficient iron-catalyzed C3-selective formylation of free (N-H) or N-substituted indoles was developed by employing formaldehyde and aqueous ammonia, with air as the oxidant. This new method gave 3-formylindoles in moderate to excellent yields with fairly short reaction times. Moreover, this procedure for catalytic formylation of indoles can be applied to gram-scale syntheses.
Molecular iodine mediated oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups into aldehydes
Mandrekar, Ketan S.,Tilve, Santosh G.
, p. 4152 - 4155 (2021)
The oxidative cleavage of the C-N bond of aryl and heteroaryl (dimethylamino)methyl groups is achieved by employing molecular iodine as a mild oxidizing agent under ambient conditions in the presence of a mild base. The important reaction of C3 formylation of free NH and substituted indoles containing various substituents is accomplished from the corresponding Mannich bases. This methodology can also be extended for the synthesis of aryl and other heteroaryl aldehydes and ketones. Furthermore, the usefulness of the method is successfully demonstrated on a gram scale.
Rhodium(III)-Catalyzed Regioselective Direct C4-Alkylation and C2-Annulation of Indoles: Straightforward Access to Indolopyridone
Biswas, Aniruddha,Samanta, Rajarshi
, p. 1426 - 1436 (2018)
A straightforward RhIII-catalyzed strategy was developed for the site-selective C4-alkylation and C2-annulation of indole by using electronically variable diazo esters. The transformation was accomplished with the assist of an oxime directing group at the C3 position of the indole core with wide scope and functional-group tolerance. The method directly provided an indolopyridone core. The selectivity was triggered by the reactivity of the diazo coupling partner.
Br?nsted Acid Catalyzed Homoconjugate Addition of Organotrifluoroborates to Arylated Cyclopropyl Ketones
Nguyen, Truong N.,Nguyen, Thien S.,May, Jeremy A.
, p. 3786 - 3789 (2016)
A novel and practical homoconjugate addition of alkenyl, alkynyl, heteroaryl, and aryl trifluoroborates to arylated cyclopropyl ketones to synthesize γ,γ-disubstituted ketones is reported. A preliminary mechanistic proposal involving ketone protonation, a
Cobalt-Catalyzed Enantioselective C–H Arylation of Indoles
Ackermann, Lutz,Jacob, Nicolas,Oliveira, Jo?o C. A.,Wencel-Delord, Joanna,Zaid, Yassir
, p. 798 - 806 (2022/02/03)
Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is the most obvious disconnection to construct such compounds, the direct enantioselective C–H arylation through the concomitant induction of the chiral information remains extremely challenging and uncommon. Herein, the unprecedented earth-abundant 3d-metal-catalyzed atroposelective direct arylation is reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies and DFT computation revealed an uncommon mechanism for this asymmetric transformation, with the oxidative addition being the rate- and enantio-determining step. Excellent stereoselectivities were reached (up to 96% ee), while using an unusual N-heterocyclic carbene ligand bearing an essential remote substituent. Attractive dispersion interactions along with positive C–H-π interactions exerted by the ligand were identified as key factors to guarantee the excellent enantioselection.
Effect of N-benzyl group in indole scaffold of thiosemicarbazones on the biological activity of their Pd(II) complexes: DFT, biomolecular interactions, in silico docking, ADME and cytotoxicity studies
Balakrishnan, Nithya,Haribabu, Jebiti,Eshaghi Malekshah, Rahime,Swaminathan, Srividya,Balachandran, Chandrasekar,Bhuvanesh, Nattamai,Aoki, Shin,Karvembu, Ramasamy
, (2022/01/26)
A series of N-benzyl substituted indole-based thiosemicarbazone (TSC) ligands (L4-L6) and palladium(II) TSC complexes, [Pd(L)2] (1–6) (L = monoanionic bidentate un/N-substituted indole-based TSC ligand) have been synthesized and characterized using analytical and spectroscopic tools. The exact molecular structures of L4-L6 and the complexes (2–4 and 6) were ascertained by single-crystal X-ray diffraction (XRD) method. Spectroscopic and crystallographic studies indicated that Pd(II) ion was coordinated with TSCs as monobasic bidentate ligands, forming two five-membered rings with square planar geometry. The effect of N-benzyl substitution in indole scaffold of TSCs in the complexes was studied using DFT method, and structure–activity relationships (SAR) were explored. The in silico ADME properties of the ligands and their complexes were thoroughly analyzed with respect to their lipophilicity and oral bioavailability. The complexes (1–6) exhibited strong intercalation with calf thymus DNA (CT DNA), which was examined by absorption/emission spectroscopic titrations and viscosity measurements. Similarly, the interaction of bovine serum albumin (BSA) with complexes examined using spectroscopic methods showed a strong binding between them. A better picture of various possible interactions was acquired from the molecular docking of the complexes with the targets like DNA, BSA, DNA Topoisomerase II and CASP3. In addition, in vitro cytotoxicity of the complexes was screened against two cancer (HeLa-S3 and A549) and one normal (IMR-90) cell lines. It was learnt that the N-benzyl substitution in the indole system inactivated the whole molecule by diminishing its anticancer activity. The unsubstituted indole TSC complex (2) displayed significant activity towards HeLa-S3 cells, and the results were compared with those of cisplatin. Beneficially, the active complex showed less toxicity against IMR-90 normal cells. Further, the results of AO-EB staining studies indicated that the complexes induced cell death via apoptosis pathway. The steric influence of the substituted indole moiety, its limited electronic effects and lesser stability in aqueous systems retarded the Pd(II) complexes of N-benzyl substituted indole TSCs from exhibiting their biological activities.
Synthesis, in silico studies, and evaluation of syn and anti isomers of n-substituted indole-3-carbaldehyde oxime derivatives as urease inhibitors against helicobacter pylori
Gunaratna, Medha J.,Kalatuwawege, Ishani P.,Udukala, Dinusha N.
, (2021/11/27)
Gastrointestinal tract infection caused by Helicobacter pylori is a common virulent disease found worldwide, and the infection rate is much higher in developing countries than in developed ones. In the pathogenesis of H. pylori in the gastrointestinal tract, the secretion of the urease enzyme plays a major role. Therefore, inhibition of urease is a better approach against H. pylori infection. In the present study, a series of syn and anti isomers of N-substituted indole-3-carbaldehyde oxime derivatives was synthesized via Schiff base reaction of appropriate carbaldehyde derivatives with hydroxylamine hydrochloride. The in vitro urease inhibitory activities of those derivatives were evaluated against that of Macrotyloma uniflorum urease using the modified Berthelot reaction. Out of the tested compounds, compound 8 (IC50 = 0.0516 ± 0.0035 mM) and compound 9 (IC50 = 0.0345 ± 0.0008 mM) were identified as the derivatives with potent urease inhibitory activity with compared to thiourea (IC50 = 0.2387 ± 0.0048 mM). Additionally, in silico studies for all oxime compounds were performed to investigate the binding interactions with the active site of the urease enzyme compared to thiourea. Furthermore, the drug-likeness of the synthesized oxime compounds was also predicted.
