20948-65-6Relevant academic research and scientific papers
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)
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.
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 (2018)
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.
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)
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.
Discovery, synthesis and in combo studies of Schiff’s bases as promising dipeptidyl peptidase-IV inhibitors
Abu Khalaf, Reema,Awad, Maha,Al-Essa, Luay,Mefleh, Sara,Sabbah, Dima,Al-Shalabi, Eveen,Shabeeb, Ihsan
, (2021/09/25)
Abstract: Diabetes mellitus is a main global health apprehension. Macrovascular illnesses, neuropathy, retinopathy, and nephropathy are considered some of its severe hitches. Gliptins are a group of hypoglycemic agents that inhibit dipeptidyl peptidase-IV (DPP-IV) enzyme and support blood glucose-lowering effect of incretins. In the current research, synthesis, characterization, docking, and biological evaluation of fourteen Schiff’s bases 5a–f and 9a–h were carried out. Compound 9f revealed the best in vitro anti-DPP-IV activity of 35.7% inhibition at a concentration of 100?μM. Compounds 9c and 9f with the highest in vitro DPP-IV inhibition were subjected to the in vivo glucose-lowering test using vildagliptin as a positive inhibitor. Vildagliptin, 9c, and 9f showed significant reduction in the blood glucose levels of the treated mice after 30?min of glucose administration. Moreover, induced fit docking showed that these derivatives accommodated the enzyme binding site with comparable docking scores. Schiff’s bases can serve as promising lead for the development of new DPP-IV inhibitors. Graphical Abstract: [Figure not available: see fulltext.].
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 characterization and antimicrobial potential of certain new isatin-indole molecular hybrids
Al-Wabli, Reem I.,Zakaria, Azza S.,Attia, Mohamed I.
, (2017/12/06)
Molecular hybridization has a wide application in medicinal chemistry to obtain new biologically active compounds. New isatin-indole molecular hybrids 5a-n have been synthesized and characterized by various spectroscopic tools. The in vitro antimicrobial potential of the prepared compounds 5a-n was assessed using diameter of the inhibition zone (DIZ) and minimum inhibitory concentration (MIC) assays against a panel of Gram-negative bacteria, Gram-positive bacteria and fungi. Most of the synthesized compounds 5a-n showed weak activities against Gram-negative bacteria while compounds 5b and 5c exhibited good activities against Gram-positive bacteria. On the other hand, compound 5j emerged as the most active compound towards Candida albicans (C. albicans), with an MIC value of 3.9 μg/mL, and compound 5g as the most active congener towards Asperagillus Niger (A. Niger), with an MIC value of 15.6 μg/mL. Moreover, compound 5h manifested the best anti-P. notatum effect, with an MIC value of 7.8 μg/mL, making it equipotent with compound 5g.
Diversity-Oriented Synthesis of Calothrixins and Ellipticines
Dethe, Dattatraya H.,Murhade, Ganesh M.
, p. 6953 - 6962 (2016/02/19)
The divergent synthesis of calothrixins and ellipticines has been accomplished by utilising the one-pot formation of o-diacylarenes as a key intermediate through rearrangement of o-hydroxy ketone monoacyl hydrazones by lead tetraacetate mediated oxidation. The divergent synthesis of calothrixins and ellipticines has been accomplished by utilising the one-pot formation of o-diacylarenes as a key intermediate through rearrangement of o-hydroxy ketone monoacyl hydrazones by lead tetraacetate mediated oxidation.
