192997-23-2Relevant academic research and scientific papers
Synthesis, antimycobacterial and anticancer activity of novel indole-based thiosemicarbazones
Mashayekhi, Vida,Haj Mohammad Ebrahim Tehrani, Kamaleddin,Azerang, Parisa,Sardari, Soroush,Kobarfard, Farzad
, (2021/09/08)
Based on the structural elements of bioactive indole-based compounds, a series of novel 1-substituted indole-3-carboxaldehyde thiosemicarbazones were synthesized as potential antimycobacterial and anticancer agents. The derivatives were prepared via a two
Synthesis and antimicrobial activities of new thiosemicarbazones and thiazolidinones in indole series
Benmohammed, Abdelmadjid,Djafri, Ayada,Kadiri, Mokhtaria,Khoumeri, Omar,Louail, Ahmed Amine,Rekiba, Nawel,Sehanine, Yassine,Terme, Thierry,Vanelle, Patrice
, p. 977 - 986 (2021/08/13)
Abstract: New thiosemicarbazones were synthesized in excellent yield reaction of indole derivatives with thiosemicarbazides. These thiosemicarbazones were reacted with ethyl bromoacetate to produce original heterocyclic-substituted indole derivatives possessing a 4-oxo-thiazolidine group. Analytical IR and NMR spectra and elemental analysis were performed to reveal their structures. The antimicrobial activity of all synthesized compounds was evaluated for antibacterial activity in vitro against Gram-positive and Gram-negative bacteria. Antibacterial screening data showed that two compounds demonstrated activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These preliminary results indicate that some of these newly synthesized compounds show a promising antibacterial potency. Graphic abstract: [Figure not available: see fulltext.].
Development of Novel Mitochondrial Pyruvate Carrier Inhibitors to Treat Hair Loss
Liu, Xiaoguang,Flores, Aimee A.,Situ, Lisa,Gu, Wen,Ding, Hui,Christofk, Heather R.,Lowry, William E.,Jung, Michael E.
, p. 2046 - 2063 (2021/02/16)
Herein, we report the synthesis and evaluation of novel analogues of UK-5099 both in vitro and in vivo for the development of mitochondrial pyruvate carrier (MPC) inhibitors to treat hair loss. A comprehensive understanding of the structure-activity relationship was obtained by varying four positions of the hit compound, namely, the alkyl group on the N1 position, substituents on the indole core, various aromatic and heteroaromatic core structures, and various Michael acceptors. The major discovery was that the inhibitors with a 3,5-bis(trifluoromethyl)benzyl group at the N1 position were shown to have much better activity than JXL001 (UK-5099) to increase cellular lactate production. Additionally, analogue JXL069, possessing a 7-azaindole heterocycle, was also shown to have significant MPC inhibition activity, which further increases the chemical space for drug design. Finally, more than 10 analogues were tested on shaved mice by topical treatment and promoted obvious hair growth on mice.
Discovery and synthesis of novel indole derivatives-containing 3-methylenedihydrofuran-2(3H)-one as irreversible LSD1 inhibitors
Liu, Hong-Min,Suo, Feng-Zhi,Li, Xiao-Bo,You, Ying-Hua,Lv, Chun-Tao,Zheng, Chen-Xing,Zhang, Guo-Chen,Liu, Yue-Jiao,Kang, Wen-Ting,Zheng, Yi-Chao,Xu, Hai-Wei
, p. 357 - 372 (2019/05/17)
Lysine-specific demethylase 1 (LSD1), demethylase against mono- and di - methylated histone3 lysine 4, has emerged as a promising target in oncology. More specifically, it has been demonstrated as a key promoter in acute myeloid leukemia (AML), and several LSD1 inhibitors have already entered into clinical trials for the treatment of AML. In this paper, a series of new indole derivatives were designed and synthesized based on a lead compound obtained by a high-throughput screening with our in-house compound library. Among the synthetic compounds, 9e was characterized as a potent LSD1 inhibitor with an IC50 of 1.230 μM and can inhibit the proliferation of THP-1 cells effectively. And most importantly, this is the first irreversible LSD1 inhibitor that is not derived from monoamine oxidase inhibitors. Hence, the discovery of 9e may serve as a proof of concept work for AML treatment.
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 (2019/11/11)
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.
Molecular dynamics guided development of indole based dual inhibitors of EGFR (T790M) and c-MET
Singh, Pankaj Kumar,Silakari, Om
, p. 163 - 170 (2018/05/22)
Secondary acquired mutation in EGFR, i.e. EGFR T790M and amplification of c-MET form the two key components of resistant NSCLC. Thus, previously published pharmacophore models of EGFR T790M and c-MET were utilized to screen an in-house database. On the ba
Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors
Sri Ramya,Angapelly, Srinivas,Guntuku, Lalita,Singh Digwal, Chander,Nagendra Babu, Bathini,Naidu,Kamal, Ahmed
, p. 100 - 114 (2016/12/30)
In our endeavour towards the development of potent cytotoxic agents, a series of some new curcumin inspired indole analogues, in which indole and phenyl moieties are linked on either sides of 1,5-diaryl-1,4-pentadien-3-one system have been synthesized and characterized by spectral data. All the newly synthesized analogues were tested for their cytotoxic potential against a panel of eight cancer cell lines namely, lung (A549), breast (MDA-MB-231, BT549 and 4T1), prostate (PC-3, DU145), gastric (HGC-27) and cervical (HeLa). Notably, among all the compounds tested, compounds 11c, 11d and 11f showed potent growth inhibition on PC-3 and BT549 with IC50values in the range of 3.12–6.34?μM and 4.69–8.72?μM respectively. The most active compound (11c) was also tested on RWPE-1 (normal prostate) cells and was found to be safe compared to the PC-3?cells. In tubulin polymerization assay, compounds 11c and 11f effectively inhibited microtubule assembly with IC50values of 10.21?±?0.10 and 8.83?±?0.06?μM respectively. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Moreover, DAPI and acridine orange/ethidium bromide staining studies indicated that compounds 11c and 11f can induce apoptosis in PC-3?cells. Further flow-cytometry analysis revealed that compound 11c arrests PC-3?cells in G2/M phase of the cell cycle while compound 11f treatment resulted in moderate increase in the G2/M population. Additionally, the treatment by these compounds led to the impairment of mitochondrial membrane potential (DΨm) in PC-3?cells.
Containing α - methylene - γ - butyrolactone structure of indole compounds, preparation method and application thereof
-
, (2017/08/25)
The invention discloses a novel indole compounds containing alpha-methylene-gamma-butyrolactone structures, a preparation method thereof and an application thereof serving as tubulin inhibitors in antitumor activity, and belongs to the field of medicinal
Identification of low micromolar dual inhibitors for aldose reductase (ALR2) and poly (ADP-ribose) polymerase (PARP-1) using structure based design approach
Chadha, Navriti,Silakari, Om
supporting information, p. 2324 - 2330 (2017/05/09)
Clinical studies have revealed that diabetic retinopathy is a multifactorial disorder. Moreover, studies also suggest that ALR2 and PARP-1 co-occur in retinal cells, making them appropriate targets for the treatment of diabetic retinopathy. To find the dual inhibitors of ALR2 and PARP-1, the structure based design was carried out in parallel for both the target proteins. A series of novel thiazolidine-2,4-dione (TZD) derivatives were therefore rationally designed, synthesized and their in vitro inhibitory activities against ALR2 and PARP-1 were evaluated. The experimental results showed that compounds 5b and 5f, with 2-chloro and 4-fluoro substitutions, showed biochemical activities in micromolar and submicromolar range (IC50 1.34–5.03?μM) against both the targeted enzymes. The structure-activity relationship elucidated for these novel inhibitors against both the enzymes provide new insight into the binding mode of the inhibitors to the active sites of enzymes. The positive results of the biochemical assay suggest that these compounds may be further optimized and utilized for the treatment of diabetic retinopathy.
Structure-based design of new poly (ADP-ribose) polymerase (PARP-1) inhibitors
Chadha, Navriti,Jaggi, Ameteshar Singh,Silakari, Om
, p. 655 - 660 (2017/08/22)
Poly (ADP-ribose) polymerase (PARP-1) is a well-established nuclear protein with prominent role in signaling and DNA repair. Various clinical candidates have been identified with the role in PARP-1 inhibition. Based on the pharmacophoric features identified from previous studies and molecular docking interactions, thiazolidine-2,4-dione derivatives have been evaluated for their PARP inhibitory activity. From an in vitro assay, 5-((1-(4-isopropylbenzyl)-1H-indol-3-yl)methylene)thiazolidine-2,4-dione (16) was identified as a potent inhibitor having low micromolar inhibitory activity (IC50=0.74±0.25μM). Thus, a structure-based design approach utilized in the present study helped to identify thiazolidine-2,4-dione as a novel scaffold against PARP-1 for potential development of potent anticancer therapeutics.
