1747-60-0Relevant articles and documents
Pharmacological profile of 6,12-dihydro-3-methoxy-1-benzopyrano[3,4-b] [1,4]benzothiazin-6-one, a novel human estrogen receptor agonist
Jacquot, Yves,Cleeren, Anny,Laios, Ioanna,Ma, Yan,Boulahdour, Athem,Bermont, Laurent,Refouvelet, Bernard,Adessi, Gerard,Leclercq, Guy,Xicluna, Alain
, p. 335 - 341 (2002)
Pharmacological studies were carried out to characterize further the endocrinological profile and the binding mode to the estrogen receptor (ER) of 6,12-dihydro-3-methoxy-l-benzopyrano[3,4-b][1,4]benzothiazin-6-one (1). Binding experiments were conducted with highly purified recombinant human estrogen receptors hERα and β. Potent estrogenic activity of compound 1 was assessed by testing its ability to down-regulate ERs and to enhance estrogen receptor element (ERE)-dependent transcription. The latest step of our work dealt with the synthesis of the 9-fluorinated derivative 15 for ionic microscopy experiments to determine the intracellular localization of compound 1. Although 1 failed to compete with [3H]E2 for binding to both ER isoforms, evidence was reported that it interacted with hERα in MCF-7 cells (ER down-regulation/ERE-dependent luciferase induction). Hence, an appropriate conformation of the hormone binding domain, most probably conferred by co-regulators of ER, is required for the onset of an activity of the compound 1. Estrogenic activity was weak but on the order of magnitude of that of coumestrol (slightly weaker). The synthesis of the 9-methoxylated derivative 16 and its pharmacological evaluation led us to propose a binding mode of 1 on hERα. Compound 1 appears to interact with ERα mainly through interactions of its 3-methoxy substituent with the residue His-524 of the hormone binding domain.
Design, synthesis, and AChE inhibitory activity of new benzothiazole–piperazines
Demir ?zkay, ümide,Can, ?zgür Devrim,Sa?l?k, Begüm Nurpelin,Acar ?evik, Ulviye,Levent, Serkan,?zkay, Yusuf,Ilg?n, Sinem,Atl?, ?zlem
, p. 5387 - 5394 (2016)
In the current study, 14 new benzothiazole–piperazine compounds were designed to meet the structural requirements of acetylcholine esterase (AChE) inhibitors. The target compounds were synthesised in three steps. Structures of the newly synthesised compounds (7–20) were confirmed using IR,1H NMR,13C NMR, and HRMS methods. The inhibitory potential of the compounds on AChE (E.C.3.1.1.7, from electric eel) was then investigated. Among the compounds, 19 and 20 showed very good activity on AChE enzyme. Kinetics studies were performed to observe the effects of the most active compounds on the substrate–enzyme relationship. Cytotoxicity studies, genotoxicity studies, and theoretical calculation of pharmacokinetics properties were also carried out. The compounds 19 and 20 were found to be nontoxic in both of the toxicity assays. A good pharmacokinetics profile was predicted for the synthesised compounds. Molecular docking studies were performed for the most active compounds, 19 and 20, and interaction modes with enzyme active sites were determined. Docking studies indicated a strong interaction between the active sites of AChE enzyme and the analysed compounds.
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Stuckwisch
, p. 3417 (1949)
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Anticonvulsant and neurotoxicity evaluation of some 6-substituted benzothiazolyl-2-thiosemicarbazones
Yogeeswari,Sriram,Mehta,Nigam,Kumar, M. Mohan,Murugesan,Stables
, p. 1 - 5 (2005)
Various 6-substituted benzothiazolyl-2-thiosemicarbazones were synthesized and screened for anticonvulsant activity in maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. The 6-methyl benzothiazolyl-2-thiosemicarbazones showed anticonvulsant activity in both mice i.p. and rat oral MES screen. The 6-nitro benzothiazolyl thiosemicarbazone derivative 1a emerged as the most promising one with anti-MES activity in mice i.p., rat i.p. and rat p.o. evaluations. All the compounds exhibited lesser or no neurotoxicity compared to phenytoin. The isatinimino derivatives had shown better activity when compared to the benzylidene or acetophenone derivatives.
CT-DNA/HSA binding interactions and cytotoxicity activity of a new copper(II) complex
Cai, Jie-Hui,Huang, Qiu-Chan,Huang, Qiu-Ping,Qin, Li-Jin,Wei, You-Huan,Zeng, Zhen-Fang,Zheng, Guang-Jin
, (2021/09/20)
We designed and synthesized a novel copper (II) complex, [Cu(ambt)2(cnbz)2], using 2-amino-6-methoxybenzothiazole (ambt) and 2-chloro-5-nitrobenzoic acid (cnbz) as ligands. Single-crystal X-ray diffraction (XRD), IR (infrared) spectra along with elemental analysis were employed to characterize its structure. Single-crystal XRD analysis illustrated the copper (II) complex belonged to the triclinic crystal system, space group P-1 and formed mononuclear hexa-coordinated structure. Electronic absorption, fluorescence spectrum and viscosity analysis were employed to assess the binding properties of the complex with CT-DNA (calf thymus DNA), as well as HSA (human serum albumin). The calculated binding constants Ka were 5.89 × 104 M?1 and 3.31 × 106 M?1 for CT-DNA and HSA, respectively, implying that complex [Cu(ambt)2(cnbz)2] displays intercalative bindings with CT-DNA and HSA. It also statically quenched CT-DNA/HSA fluorescence. CCK-8 assay revealed that compared to cisplatin, the complex exerts greater anti-proliferative influence against HepG2, HeLa and A549 cell lines. Flow cytometry revealed that [Cu(ambt)2(cnbz)2] arrested the cycle of HepG2 cells at G0/G1 phase, inducing apoptosis / necrosis. The degree of apoptosis / necrosis and inhibition of cell cycle is dose-, as well as time-dependent.
Discovery of Potent Carbonic Anhydrase Inhibitors as Effective Anticonvulsant Agents: Drug Design, Synthesis, and in Vitro and in Vivo Investigations
Mishra, Chandra Bhushan,Kumari, Shikha,Angeli, Andrea,Bua, Silvia,Mongre, Raj Kumar,Tiwari, Manisha,Supuran, Claudiu T.
, p. 3100 - 3114 (2021/04/12)
Two sets of benzenesulfonamide-based effective human carbonic anhydrase (hCA) inhibitors have been developed using the tail approach. The inhibitory action of these novel molecules was examined against four isoforms: HCA I, hCA II, hCA VII, and hCA XII. Most of the molecules disclosed low to medium nanomolar range inhibition against all tested isoforms. Some of the synthesized derivatives selectively inhibited the epilepsy-involved isoforms hCA II and hCA VII, showing low nanomolar affinity. The anticonvulsant activity of selected sulfonamides was assessed using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (sc-PTZ) in vivo models of epilepsy. These potent CA inhibitors effectively inhibited seizures in both epilepsy models. The most effective compounds showed long duration of action and abolished MES-induced seizures up to 6 h after drug administration. These sulfonamides were found to be orally active anticonvulsants, being nontoxic in neuronal cell lines and in animal models.
