2564-02-5Relevant academic research and scientific papers
Structure guided design and synthesis of furyl thiazolidinedione derivatives as inhibitors of GLUT 1 and GLUT 4, and evaluation of their anti-leukemic potential
Aguilera, Renato J.,Choe, Jun-yong,Hess, Jessica D.,Iancu, Cristina V.,Macias, Lucasantiago Henze,Meyer-Almes, Franz-Josef,Mrowka, Piotr,Ramaa, C. S.,Tilekar, Kalpana,Upadhyay, Neha
, (2020)
Cancer cells increase their glucose uptake and glycolytic activity to meet the high energy requirements of proliferation. Glucose transporters (GLUTs), which facilitate the transport of glucose and related hexoses across the cell membrane, play a vital ro
Discovery of 5-naphthylidene-2,4-thiazolidinedione derivatives as selective HDAC8 inhibitors and evaluation of their cytotoxic effects in leukemic cell lines
J?nsch, Niklas,Meyer-Almes, F. J.,Mrowka, Piotr,Ramaa, C. S.,Schweipert, Markus,Tilekar, Kalpana,Upadhyay, Neha
, (2020)
Histone deacetylases (HDACs) are being explored as a therapeutic target for interventions in different types of cancer. HDAC8 is a class I HDAC that is implicated as a therapeutic target in various indication areas, including different types of cancer and particularly childhood neuroblastoma. Most previously described HDAC8-selective inhibitors contain a hydroxamate function as zinc binding group (ZBG) to confer potency. However, hydroxamate class HDAC inhibitors have raised increasing concerns about their mutagenic character. Therefore, non-hydroxamate based inhibitors could prove to be safer than hydroxamates. In the present work, a series of novel 5-naphthylidene-2,4-thiazolidinedione was designed and evaluated as potential antiproliferative agents targeting selectively HDAC8 enzyme. Eleven novel derivatives were synthesized, purified and characterized by spectroscopic techniques. Compounds 3k and 3h was found to be most potent selective inhibitors of HDAC8 with IC50 values of 2.7 μM and 6.3 μM respectively. 3a to 3i was found to be most cytotoxic in leukemic cell lines. 3a and 3 h both were found to induce apoptosis and cause cell cycle arrest in G2/M phase.
Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors
Liu, Mei-Ling,Li, Wei-Yi,Fang, Hai-Lian,Ye, Ya-Xi,Li, Su-Ya,Song, Wan-Qing,Xiao, Zhu-Ping,Ouyang, Hui,Zhu, Hai-Liang
, (2021/11/13)
Thirty-eight disulfides containing N-arylacetamide were designed and synthesized in an effort to develop novel urease inhibitors. Biological evaluation revealed that some of the synthetic compounds exhibited strong inhibitory potency against both cell-free urease and urease in intact cell with low cytotoxicity to mammalian cells even at concentration up to 250 μM. Of note, 2,2′-dithiobis(N-(2-fluorophenyl)acetamide) (d7), 2,2′-dithiobis(N-(3,5-difluorophenyl)acetamide) (d24), and 2,2′-dithiobis(N-(3-fluorophenyl)acetamide) (d8) were here identified as the most active inhibitors with IC50 of 0.074, 0.44, and 0.81 μM, showing 32- to 355-fold higher potency than the positive control acetohydroxamic acid. These disulfides were confirmed to bind urease without covalent modification of the cysteine residue and to inhibit urease reversibly with a mixed inhibition mechanism. They also showed very good anti-Helicobacter pylori activities with d8 showing a comparable potency to the clinical used drug amoxicillin. The impressive in vitro biological profile indicated their immense potential as therapeutic agents to tackle H. pylori caused infections.
Discovery of a Potent Botulinum Neurotoxin A Inhibitor ZM299 with Effective Protections in Botulism Mice
Gao, Jie,He, Zhili,Hong, Zhanying,Li, Tao,Luo, Deyan,Miao, Zhenyuan,Ning, Nianzhi,Wang, Hui,Wang, Jianxin,Wu, Yuelin,Xv, Xiguo,Zhang, Wannian,Zhang, Yanming,Zhuang, Chunlin
, p. 357 - 364 (2021/12/24)
Botulinum neurotoxins serotype A (BoNT/A) is the deadliest toxins known to humans and the "Category A" agent for bioterrorism. Over the past 20 years, significant efforts have been put forth to develop effective inhibitors of BoNT/A. Unfortunately, few id
Synthesis, molecular modeling, selective aldose reductase inhibition and hypoglycemic activity of novel meglitinides
Salem, Manar G.,Abdel Aziz, Yasmine M.,Elewa, Marwa,Nafie, Mohamed S.,Elshihawy, Hosam A.,Said, Mohamed M.
, (2021/04/29)
In the present study, a novel generation of selective aldose reductase ALR2 inhibitors with significant hypoglycemic activities was designed and modulated based on rhodanine scaffold joined to an acetamide linker in between two lipophilic moieties. The synthesis of the novel compounds was accomplished throughout simple chemical pathways. Molecular docking was performed on B-cell membrane protein SUR1, aldehyde reductase ALR1 and aldose reductase ALR2 active sites. Compounds 10B, 11B, 12B, 15C, 16C, 26F and 27F displayed the highest hypoglycemic activities with 80.7, 85.2, 87, 82.3, 83.5, 81.4 and 85.3% reduction in blood glucose levels, respectively. They were more potent than the standard hypoglycemic agent repaglinide with 65.4% reduction in blood glucose level. Compounds 12B and 15C with IC50 0.29 and 0.35 μM were more potent than the standard ALR2 inhibitor epalrestat with IC50 0.40 μM. They were selective towards ALR2 over ALR1 134 and 116 folds, respectively. Molecular docking studies matched with the in-vitro and in-vivo results to elucidate the dual activities of both compounds 12B and 15C as potent antagonists for ALR2 over ALR1 and good agonists for the SUR1 protein.
Novel fluoroquinolones containing 2-arylamino-2-oxoethyl fragment: Design, synthesis, evaluation of antibacterial and antituberculosis activities and molecular modeling studies
Bozdeveci, Arif,Krishna, Vagolu Siva,Sriram, Dharmarajan,Alpay Karao?lu, ?engül,Kü?ükgüzel, ?lkay,Kulaba?, Necla,Türe, Asl?
, (2022/01/11)
Novel substituted fluoroquinolone derivatives, compounds 6–20 were designed, synthesized, and evaluated for antituberculosis and antibacterial activity. Antibacterial activities of the compounds were determined and compound 14 was found to be the most pot
Anti-melanogenesis and anti-tyrosinase properties of aryl-substituted acetamides of phenoxy methyl triazole conjugated with thiosemicarbazide: Design, synthesis and biological evaluations
Hosseinpoor, Hona,Moghadam Farid, Sara,Iraji, Aida,Askari, Sadegh,Edraki, Najmeh,Hosseini, Samanesadat,Jamshidzadeh, Akram,Larijani, Bagher,Attarroshan, Mahshid,Pirhadi, Somayeh,Mahdavi, Mohammad,Khoshneviszadeh, Mehdi
, (2021/06/21)
A series of aryl phenoxy methyl triazole conjugated with thiosemicarbazides were designed, synthesized, and evaluated for their tyrosinase inhibitory activities in the presence of L-dopa and L-tyrosine as substrates. All the compounds showed tyrosinase inhibition in the sub-micromolar concentration. Among the derivatives, compound 9j bearing benzyl displayed exceptionally high potency against tyrosinase with IC50 value of 0.11 μM and 0.17 μM in the presence of L-tyrosine and L-dopa as substrates which is significantly lower than that of kojic acid as the positive control with an IC50 value of 9.28 μM for L-tyrosine and 9.30 μM for L-dopa. According to Lineweaver–Burk plot, 9j demonstrated an uncompetitive type of inhibition in the kinetic assay. Also, in vitro antioxidant activities determined by DPPH assay recorded an IC50 value of 68.43 μM for 9i. The melanin content of 9j was determined on B16F10 melanoma human cells which demonstrated a significant reduction of the melanin content. Moreover, the binding energies corresponding to the same ligand as well as computer-aided drug-likeness and pharmacokinetic studies were also carried out. Compound 9j also possessed metal chelation potential correlated to its high anti-TYR activity.
Synthesis, pharmacological evaluation, and in-silico studies of thiophene derivatives
Mishra, Raghav,Kumar, Nitin,Sachan, Neetu
, (2021/12/23)
The relevance of Retinoic acid receptor-related orphan receptors in cancer progression has sparked interest in developing multifunctional therapeutics. In the search for potentially active novel compounds with anticancer characteristics, the Gewald reaction was employed to develop different thiophene derivatives (8a–8i). Physicochemical and spectroanalytical investigations verified the molecular structures of the synthesized derivatives. Using an in vitro primary anticancer assay, NCI chose all of the synthesized molecules as prototypes and assessed their anticancer efficacy against a panel of various cancer cell lines representing nine distinct neoplasms. The compounds were found to have a wide range of anticancer activity. Following significant anticancer efficacy against all cell lines in the initial screening, compound 8e was chosen for a five-dose test. Compound 8e inhibited growth at concentrations ranging from 0.411 to 2.8 μM. The antioxidant activity of the compounds was further evaluated using the radical scavenging action of the stable DPPH free radical. In comparison to Ascorbic Acid, compounds 8e and 8i showed outstanding antioxidant activity, while the remaining compounds in the series demonstrated acceptable antioxidant activity. In a molecular docking investigation, 8e demonstrated excellent docking scores inside the binding pocket of the specified pdb-id (6q7a), complementing the results of anticancer screening. Based on our results, novel ethyl 5-acetyl-2-amino-4-methylthiophene-3-carboxylate derivatives could be useful in the development of potential anticancer treatments.
Novel pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety: design, synthesis, molecular docking, and biological evaluation as potential multi-target cytotoxic agents
Shawky, Ahmed M.,Ibrahim, Nashwa A.,Abdalla, Ashraf N.,Abourehab, Mohammed A. S.,Gouda, Ahmed M.
, p. 1313 - 1333 (2021/06/25)
In the present study, two new series of pyrrolizines bearing 3,4,5-trimethoxyphenyl moiety were designed, synthesised, and evaluated for their cytotoxic activity. The benzamide derivatives 16a–e showed higher cytotoxicity than their corresponding Schiff b
Novel 1,2,4-triazole analogues as mushroom tyrosinase inhibitors: synthesis, kinetic mechanism, cytotoxicity and computational studies
Vanjare, Balasaheb D.,Mahajan, Prasad G.,Dige, Nilam C.,Raza, Hussain,Hassan, Mubashir,Han, Yohan,Kim, Song Ja,Seo, Sung-Yum,Lee, Ki Hwan
, p. 2089 - 2106 (2020/05/18)
We have created a novel series of mushroom tyrosinase inhibitors with 1,2,4-triazole as fundamental skeleton. The target compound 1,2,4-triazol-3-ylthio)-N-phenyl acetamide derivatives 9(a–l) were synthesized by the reaction of 4- and 5-substituted 1,2,4-triazole-3-thiol derivatives 6(a–c) with 2-chloro-N-sub/un-substituted phenyl acetamide derivatives 8(a–d) under basic condition. By using the analytical techniques for instance, FTIR, LC–MS, 1H NMR and 13C NMR, the structural verification was evaluated. The novel series of the target compounds 9(a–l) has been scanned for biological activity (mushroom tyrosinase inhibition potential) which demonstrates adequate results. Interestingly, compound 9k (IC50 = 0.0048 ± 0.0016?μM) exhibits 3500 times more activity compared with standard drug kojic acid (IC50 = 16.8320 ± 1.1600?μM) against mushroom tyrosinase inhibitor. Furthermore, the cytotoxicity experiment was carried out for the highly effective target compounds (9d, 9i, 9j and 9k) by using MTT assay method for A375 human melanoma cells to define the nontoxic performance of the most effective compounds ranging from 1 to 25?μM. Furthermore, the molecular docking study delivers the thought concerning the interface of the ligand with an enzyme. Also, the dynamic simulation was accomplished for compound 9k to govern the plausible binding model.
