- Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents
-
A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5g and 5n were emerged as the most active compounds of the series with MIC of 0.8 μg/mL (~1.9 μM). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 μg/mL), and compounds 5j, 5k and 5o (MIC = 3.125 μg/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/npropyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121.
- Ramprasad, Jurupula,Nayak, Nagabhushana,Dalimba, Udayakumar
-
-
Read Online
- A novel route to 1,2,4-triazoles
-
A novel synthetic method for the synthesis of 1,2,4-triazoles have been described starting from 1,3,4-thiadiazoles by adsorbing on acidic alumina under microwave irradiations (MWI).
- Kidwai, Mazaahir,Misra, Preeti,Bhushan, Kumar Ranjan,Dave, Bhavesh
-
-
Read Online
- Synthesis, extraction, and transport properties of dibenzo-18-crown-6 modified with the fragments of 2-amino-1,3,4-thiadiazol and kojic acid
-
New heterocyclic derivatives of dibenzo-18-crown-6 (DB18C6), the products of coupling of kojic acid (5-hydroxy-2-hydroxymethyl-γ-pyrone) with 4′-DB18C6-yldiazonium chloride, 4′,4″-and 4′,5′- DB18C6-diyldiazonium dichlorides and products of heterocyclization of DB18C6 mono-and dicarboxylic acids with thiosemicarbazide are prepared. Their structures are studied by the methods of 1H NMR and IR spectroscopy. Polyphosphoric acid is found to be the best agent for the heterocyclization of thiosemicarbazide with DB18C6 carboxylic derivatives. It is proven that the parent substrates, the DB18C6 mono or dicarboxylic acids, serve as phase transfer catalysts for the heterocyclization reaction. Extraction and transport properties of the obtained compounds in respect of potassium, sodium and ammonium picrates are explored.
- Kuznetsov,Kuznetsova,Kadirova,Reshetnikova,Tashmukhamedova
-
-
Read Online
- Facile synthesis, spectral studies, DFT calculations and biological activities of novel NI (II), CU (II), and PD (II) complexes of thiadiazole analogs
-
Objective: A facile synthesis of some novel Schiff base derivatives of 2-substituted-5-amino-thiadiazoles along with their Ni (II), Cu (II), and Pd (II) complexes were achieved by sonication and the conventional method. In addition to establish the structure by DFT studies and to explore antimicrobial and anticancer activities of these novel compounds. Methods: The precursor 2-substituted-5-amino-thiadiazoles (T1-T3), target ligands and their metal complexes were synthesized by ultrasonication and conventional means. The isolated products were thoroughly characterized by physical and spectroscopic techniques including1H-NMR,13C-NMR and IR spectroscopy. All characterized compounds were screened for antimicrobial activities using well diffusion method, and MTT assay was performed for cytotoxicity. Results: All novel compounds were synthesized by a green route i.e. ultra sonication and a noticeable improvement in yield with shorter reaction time than the conventional method were observed. The octahedral geometry was proposed for Ni (II)/Cu (II) complexes whereas square planar for Pd (II) complexes on the basis of the spectral techniques which were supported by DFT analysis by Gaussian03. On the analysis of antimicrobial activities, the compound T7 and T10 showed maximum antibacterial and antifungal activities respectively. However, compounds T25, T37, T31 found to be a potential cytotoxic compound with IC50 value 0.469, 0.865 and 1.131 μM respectively. Conclusion: Analysis of synthetic protocol, it could be concluded that ultra-sonication is the better method to synthesize these potential biological active moiety. On the whole Cu (II) and Ni (II) complexes showed promising activity towards all microorganisms while Pd (II) complex emerged an excellent moiety in carcinoma cell line.
- Bhatt, Priyanka,Deepthi,Ravi Shankar Kumar, Ch,Jha, Anjali
-
-
Read Online
- Rapid synthesis, characterization, anticancer and antimicrobial activity studies of substituted thiadiazoles and their dinucleating ligand metal complexes
-
Synthesis of 2,5-disubstituted thiadiazoles was accomplished via a conventional method as well as microwave irradiation method. These substituted thiadiazoles were diazotized and coupled with 2,4-pentanedione (AcAc), ethylcyanoacetate (ECA) and malanodinitrile (MN) to get dinucleating ligands. The ligands were isolated, characterized and condensed with Ni (II), Cu (II) and Ru(III) chlorides. These compounds were screened on HL-60 Human leukemia cell Line and U-937 Lymphoma cell lines for anticancer activities. The antimicrobial activity of the ligands and their complexes against bacteria and fungi was also investigated. The effect of metal on the ligand activity is discussed. Springer Science+Business Media, LLC 2011.
- Jha, Anjali,Murthy,Sanyal,Durga
-
-
Read Online
- Acetazolamide-based fungal chitinase inhibitors
-
Chitin is an essential structural component of the fungal cell wall. Chitinases are thought to be important for fungal cell wall remodelling, and inhibition of these enzymes has been proposed as a potential strategy for development of novel anti-fungals. The fungal pathogen Aspergillus fumigatus possesses two distinct multi-gene chitinase families. Here we explore acetazolamide as a chemical scaffold for the inhibition of an A. fumigatus 'plant-type' chitinase. A co-crystal structure of AfChiA1 with acetazolamide was used to guide synthesis and screening of acetazolamide analogues that yielded SAR in agreement with these structural data. Although acetazolamide and its analogues are weak inhibitors of the enzyme, they have a high ligand efficiency and as such are interesting leads for future inhibitor development.
- Schüttelkopf, Alexander W.,Gros, Ludovic,Blair, David E.,Frearson, Julie A.,Van Aalten, Daan M.F.,Gilbert, Ian H.
-
-
Read Online
- Synthesis, characterization and biological evaluation of some novel fluoroquinolones
-
Different derivatives of fluoroquinolones were synthesized by combining it with different thiadiazoles. The synthesized compounds were characterized by infrared spectroscopy, proton nuclear magnetic resonance and mass spectral data. The compounds were screened for their antibacterial and antifungal activity. Ciprofloxacin derivatives with thiadiazoles 7c showed good antibacterial as well as antifungal activities, whereas 13c and 13e showed antibacterial and antifungal activity respectively. Sparfloxacin derivative 8c showed both antibacterial and antifungal activity. Sparfloxacin derivatives 14b and 14e showed antibacterial and antifungal activity respectively.
- Pandit, Neelanjana,Shah, Kamal,Agrawal, Neetu,Upmanyu, Neeraj,Shrivastava, Sushant K.,Mishra, Pradeep
-
-
Read Online
- Pd2(dba)3-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4] thiadiazole with substituted anilines at conventional heating in Schlenk tube
-
An efficient Pd2(dba)3-catalyzed amination of C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole using conventional heating is reported. The C5-bromoimidazo[2,1-b][1,3,4]thiadiazole was synthesized using a multistep approach which started by cyclization of thiosemicarbazide with a carboxylic acid to give 2-amino[1,3,4]thiadiazoles which were further treated with 2-haloketones to give imidazo[2,1-b][1,3,4]thiadiazoles. Then, the bromination of imidazothiadiazole was done using N-bromosuccinimide to give the C5-bromo-imidazo[2,1-b][1,3,4]thiadiazole. Afterward, various C-N bond-forming approaches were attempted such as SNAr, Cu(I), Cu(II), Pd(OAc)2, Pd2(dba)3 catalyst with different ligand, additive, base, solvent and temperature conditions. Out of various approaches used, only Buchwald Hartwig amination, performed with conventional heating, gave N-arylamine-5-imidazothiadiazoles. Then, 10 different anilines with different electron-withdrawing and donating groups at different positions were employed to examine the scope and limitations of the method. Salient features of this method include conventional heating in a Schlenk tube as the reaction condition, the absence of the use of toxic isocyanides, the wide nature of substituent tolerance with anilines, and moderately good product yields.
- Rawat, Ravi,Verma, Saurabh M.
-
-
Read Online
- Synthesis and antifungal activity of thiadiazole-functionalized chitosan derivatives
-
A groups of novel water soluble chitosan derivatives containing 1,3,4-thiadiazole group were synthesized including 1,3,4-thiadiazole (TPCTS), 2-methyl-1,3,4-thiadiazole (MTPCTS), and 2-phenyl-1,3,4-thiadiazole (PTPCTS). Their antifungal activity against three kinds of phytopathogens was estimated by hypha measurement in vitro, and the fungicidal assessment shows that the synthesized chitosan derivatives have excellent activity against tested fungi. Of all the synthesized chitosan derivatives, MTPCTS inhibited the growth of the tested phytopathogens most effectively with inhibitory indices of 75.3%, 82.5%, and 65.8% against Colletotrichum lagenarium (Pass) Ell.et halst, Phomopsis asparagi (Sacc.) Bubak, and Monilinia fructicola (Wint.) Honey respectively at 1.0 mg/mL. These indices are higher than those of chitosan. These data also demonstrate that the hydrophobic moiety (alkyl and phenyl) and the length of alkyl substituent in thiadiazole tend to affect the antifungal activity of chitosan derivatives. It is hypothesized that thiadiazole groups enable the synthesized chitosan to possess obviously better antifungal activity and good solubility in water.
- Li, Qing,Ren, Jianming,Dong, Fang,Feng, Yan,Gu, Guodong,Guo, Zhanyong
-
-
Read Online
- A synthetic approach, characterization and biological evaluation of novel 5-(Arylidene)-2-(5-methyl-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives
-
The extensive biological potential of thiazolidin-4-one and 1,3,4-thiadiazole moieties, the novel string of 5-(arylidene)-2-(5-methyl-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one has been synthesized and characterized. The synthesized derivatives were screened for antimicrobial potential using serial tube dilution method. The results showed that all the synthesized compounds have significant biological activity against the microorganisms being tested. The antimicrobial activity of the compounds TA2, TA3, TA4, TA9, TA10 and TA20 against the tested microbial strains was promising. Compound TA4 (2-((5-methyl-1,3,4-thiadiazol-2-yl)imino)-5-(4-nitrobenzylidene)- thiazolidin-4-one) and TA2 (5-(4-chlorobenzylidene)-2-((5-methyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one) showed promising antimicrobial activity against microbial strains. Compound TA9 (5-(4-(benzyloxy)benzylidene)-2-((5-methyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one) was found to be the most effective towards B. subtilis. Compound TA10 (5-(3,4-dimethoxybenzylidene)-2-((5-methyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one) was discovered to be the most potent against the Gram-negative bacteria. Compounds TA3 (5-(4-bromobenzylidene)-2-((5-methyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one) and TA20 (5-(2-bromobenzylidene)-2-((5-methyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one) were the most effective compounds against the fungal strain.
- Aggarwal, Navidha,Jain, Sandeep
-
p. 1530 - 1536
(2021/07/02)
-
- Synthesis of Emodin Amide Derivatives Containing 1,3,4-Thiadiazole and Their Inhibitory Activity on Vibrio harveyi
-
A series of new 1,3,4-thiadiazole Emodin amide derivatives were synthesized through the connection of 5-substituted-1,3,4-thiadiazole-2-amine and Emodin carboxylic acids which were obtained by a two-step procedure starting from Emodin. Vibrio harveyi inhibition activities of the newly prepared compounds were evaluated. Results revealed that all compounds showed different degrees of inhibition on V. harveyi. Among them, compound 7a showed the best V. harveyi inhibition effect and the minimum inhibitory concentration (MIC) was 0.0625 mg/mL.
- Cao, Lian-Gong,Cao, Zhi-Ling,Chen, Chao,Jiang, Kai-Jun,Liu, Shu-Hao,Liu, Wei-Wei,Ruan, Xin-Chi,Shao, Zhong-Bai,Shi, Da-Hua,Su, Zi-Qin,Wang, You-Xian,Wu, Yu-Ran,Wu, Yu-Yu
-
p. 281 - 286
(2021/08/05)
-
- Preparation of 1,3,4-oxadiazoles and 1,3,4-thiadiazoles via chemoselective сyclocondensation of electrophilically activated nitroalkanes to (thio)semicarbazides or thiohydrazides
-
[Figure not available: see fulltext.] Unusual reaction proceeding via the electrophilic activation of nitroalkanes in the presence of polyphosphoric acid has been discovered. Subsequent nucleophilic attack with semicarbazides or thiosemicarbazides allows
- Aksenov, Alexander V.,Aksenov, Dmitrii A.,Aksenov, Nicolai A.,Arutiunov, Nikolai A.,Kirillov, Nikita K.,Rubin, Michael
-
p. 1067 - 1072
(2020/10/02)
-
- Method for preparing 2-amino-5-substituted-1,3,4-thiadiazole
-
The invention relates to a method for preparing 2-amino-5-substituted-1,3,4-thiadiazole, The method comprises: adding choline chloride and urea into a reaction container according to a formula ratio,and stirring at 80 DEG C to obtain a colorless transparent solution, ie., a eutectic solvent DES; cooling to a room temperature, adding carboxylic acid and thiosemicarbazide according to a formula ratio, slowly heating, reacting at 80 DEG C, and carrying out TLC monitoring until the reaction is finished; cooling the reaction mixed liquid to a room temperature, adding ammonia water into the mixed liquid under ice bath cooling to adjust the pH value to 8-9, precipitating the solid, carrying out suction filtration, washing the filter cake with ice water, and drying to obtain the 2-amino-5-substituted-1,3,4-thiadiazole; and recovering the filtrate to obtain the eutectic solvent capable of being repeatedly used. According to the invention, the method has characteristics of simple operation, simple post-treatment, short reaction time, high efficiency, catalyst recycling, environmental protection, cost reducing and no requirement of organic solvents, and is a method for efficiently synthesizing 2-amino-5-substituted-1,3,4-thiadiazole.
- -
-
Paragraph 0038-0044
(2020/02/14)
-
- Synthesis of (1,3,4-thiadiazol-2-yl)-acrylamide derivatives as potential antitumor agents against acute leukemia cells
-
A lead compound with the (1,3,4-thiadiazol-2-yl)-acrylamide scaffold was discovered to have significant cytotoxicity on several tumor cell lines in an in-house cell-based screening. A total of 60 derivative compounds were then synthesized and tested in a CCK-8 cell viability assay. Some of them exhibited improved cytotoxic activities. The most potent compounds had IC50 values of 1–5 μM on two acute leukemia tumor cell lines, i.e. RS4;11 and HL-60. Flow cytometry analysis of several active compounds and detection of caspase activation indicated that they induced caspase-dependent apoptosis. It was also encouraging to observe that these compounds did not have obvious cytotoxicity on normal cells, i.e. IC50 > 50 μM on HEK-293T cells. Although the molecular targets of this class of compound are yet to be revealed, our current results suggest that this class of compound represents a new possibility for developing drug candidates against acute leukemia.
- An, Ran,Guo, Chun,Li, Qing,Li, Yan,Wang, Renxiao,Xu, Yaochun,Zhou, Mi
-
supporting information
(2020/03/25)
-
- Further insight into the dual COX-2 and 15-LOX anti-inflammatory activity of 1,3,4-thiadiazole-thiazolidinone hybrids: The contribution of the substituents at 5th positions is size dependent
-
Herin we report the design, synthesis, full characterization and biological investigation of new 15-LOX/COX dual inhibitors based on 1,3-thiazolidin-4-one (15-lipoxygenase pharmacophore) and 1,3,4-thiadiazole (COX pharmacophore) scaffolds. This series of molecular modifications is an extension of a previously reported series to further explore the structural activity relationship. Compounds 3a, 4e, 4n, 4q, 7 and 8 capable of inhibiting 15-LOX at (2.74, 4.2, 3.41, 10.21, 3.71 and 3.36 μM, respectively) and COX-2 at (0.32, 0.28, 0.28, 0.1, 0.28 and 0.27 μM, respectively). The results revealed that binding to 15-LOX and COX is sensitive to the bulkiness of the substituents at the 5 positions. 15-LOX bind better with small substituents, while COXs bind better with bulky substituents. Compounds 3a, 4r and 4q showed comparable in vivo anti-inflammatory activity to the reference drug (celecoxib). The ulcer liability test showed no sign of ulceration which ensures the safe gastric profile. Docking study was performed to explore the possible mode of interaction of the new compounds with the active site of human 15-LOX and COX-2. This study discloses some structural features for binding to 15-LOX and COX, thus pave the way to design anti-inflammatory agents with balanced dual inhibition of these enzymes.
- Abdel-Moty, Samia G.,Abdu-Allah, Hajjaj H. M.,Omar, Yasser M.
-
-
- Discovery of novel nonpeptide small-molecule NRP1 antagonists: Virtual screening, molecular simulation and structural modification
-
Multifaceted roles of vascular endothelial growth factor (VEGF)-neuropilin-1 (NRP1) interaction have been implicated in cancer, but reports on small-molecule inhibitors of VEGF-NRP1 interaction are scarce. Herein, we describe the identification of 1, a novel nonpeptide small-molecule NRP1 antagonist with moderate activity via structure-based virtual screening. Ensemble docking and molecular dynamics (MD) simulations of 1 were carried out and an interesting binding model was obtained. We found that the “aromatic box” enclosed by Tyr297, Trp301 and Tyr353 of NRP1 is critical for NRP1-1 binding. Further structure modification of 1 based on the binding model derived from MD simulations resulted in the identification of 12a with significantly improved activity.
- Peng, Kewen,Li, Yu,Bai, Ying,Jiang, Teng,Sun, Huiyong,Zhu, Qihua,Xu, Yungen
-
-
- N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides bearing heteroaromatic rings as novel antibacterial agents: Design, synthesis, biological evaluation and target identification
-
Due to the occurrence of antibiotic resistance, bacterial infectious diseases have become a serious threat to public health. To overcome antibiotic resistance, novel antibiotics are urgently needed. N-thiadiazole-4-hydroxy-2-quinolone-3-carboxamides are a potential new class of antibacterial agents, as one of its derivatives was identified as an antibacterial agent against S. aureus. However, no potency-directed structural optimization has been performed. In this study, we designed and synthesized 37 derivatives, and evaluated their antibacterial activity against S. aureus ATCC29213, which led to the identification of ten potent antibacterial agents with minimum inhibitory concentration (MIC) values below 1 μg/mL. Next, we performed bacterial growth inhibition assays against a panel of drug-resistant clinical isolates, including methicillin-resistant S. aureus, and cytotoxicity assays with HepG2 and HUVEC cells. One of the tested compounds named 1-ethyl-4-hydroxy-2-oxo-N-(5-(thiazol-2-yl)-1,3,4-thiadiazol-2-yl)-1,2-dihydroquinoline-3-carboxamide (g37) showed 2 to 128-times improvement compared with vancomycin in term of antibacterial potency against the tested strains (MICs: 0.25–1 μg/mL vs. 1–64 μg/mL) and an optimal selective toxicity (HepG2/MRSA, 110.6 to 221.2; HUVEC/MRSA, 77.6–155.2). Further, comprehensive evaluation indicated that g37 did not induce resistance development of MRSA over 20 passages, and it has been confirmed as a bactericidal, metabolically stable, orally active antibacterial agent. More importantly, we have identified the S. aureus DNA gyrase B as its potential target and proposed a potential binding mode by molecular docking. Taken together, the present work reports the most potent derivative of this chemical series (g37) and uncovers its potential target, which lays a solid foundation for further lead optimization facilitated by the structure-based drug design technique.
- Xue, Wenjie,Li, Xueyao,Ma, Guixing,Zhang, Hongmin,Chen, Ya,Kirchmair, Johannes,Xia, Jie,Wu, Song
-
-
- Metal-free synthesis of 2-aminothiadiazoles via TBHP-Mediated oxidative C-S bond formation
-
An efficient one-pot synthesis of 2-amino-1,3,4-thiadiazoles from easily available aldehydes and thiosemicarbazide using TBHP as an oxidant has been described. Notably, these reactions were carried out at room temperature using ethanol as solvent. This is the first example for one-pot synthesis of 2-amino-1,3,4-thiadiazole derivatives from aldehydes. This new synthetic methodology provides a simple procedure utilizing a safer oxidizing system that affords the target products in mild reaction condition with satisfactory yields and wide substrate scope.
- Hatvate, Navnath T.,Ghodse, Shrikant M.,Telvekar, Vikas N.
-
supporting information
p. 285 - 290
(2018/02/09)
-
- 2-methyl-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method
-
The present invention discloses a 2-methyl-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method, which comprises: carrying out stirring mixing on 2-amino-5-methyl-1,3,4-thiadiazole, alpha-bromo-acetylferrocene and ethanol; placing the mixed solution in a microwave oven, and carrying out microwave irradiation; after the alpha-bromo-acetylferrocene completely reacts, carrying out a microwave reaction; adding water to the reaction solution, and adjusting the pH value of the reaction solution to 7-8 with a saturated sodium carbonate solution; carrying out suction filtration, washing the filter cake with water, and drying to obtain a crude product; and re-crystallizing with DMF to obtain the target product. According to the present invention, the microwave-assisted synthesis reaction is used so as to substantially shorten the reaction time and improve the reaction efficiency.
- -
-
Paragraph 0024; 0028; 0029; 0039; 0050
(2018/01/12)
-
- Preparation of 2-amino-5-alkyl -1, 3, 4-thiadiazole
-
The invention discloses a method for preparing 2-amino-5-alkyl-1,3,4-thiadiazole. The method comprises the following steps of adding A mol of thiosemicarbazide, B mol of carboxylic acid, C mol of phosphorus oxychloride and D mol of silica gel in a dry reaction container, grinding at a room temperature until the raw materials are completely reacted, and standing to obtain a crude product, wherein A: B: C = 1: (1 to 1.2): (1 to 1.2), and A: D = 1: (5 to 10); then adding alkaline solution in the crude product until the pH value of the obtained mixed solution is 8-8.2, then carrying out suction filtration on the mixed solution, dissolving the filter cake by a solvent and then further carrying out suction filtration, removing silica gel, then carrying out reduced pressure concentration on the finally-obtained filtrate, and removing the solvent to obtain 2-amino-5-alkyl-1,3,4-thiadiazole. The method disclosed by the invention is a solid-phase reaction, silica gel is used as a carrier, the operation process is simple, the reaction time is short, the reaction conditions are moderate, the equipment requirements are low, and the yield of the target product is up to more than 91%.
- -
-
Paragraph 0024-0026
(2017/04/19)
-
- Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study
-
Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl but also other acyl groups from the ε-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 (hSirt2) activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, which makes the modulation of hSirt2 activity a promising strategy for pharmaceutical intervention. The sirtuin rearranging ligands (SirReals) have recently been discovered by us as highly potent and isotype-selective hSirt2 inhibitors. Here, we present a well-defined structure-activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the hSirt2 targeted tubulin caused by our improved lead structure.
- Schiedel, Matthias,Rumpf, Tobias,Karaman, Berin,Lehotzky, Attila,Oláh, Judit,Gerhardt, Stefan,Ovádi, Judit,Sippl, Wolfgang,Einsle, Oliver,Jung, Manfred
-
p. 1599 - 1612
(2016/03/05)
-
- Ionic liquid-promoted one-pot synthesis of thiazole-imidazo[2,1-b][1,3,4]thiadiazole hybrids and their antitubercular activity
-
In this paper, we report the facile and efficient one-pot three-component synthesis of 1-((6-phenylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)-2-(4-phenylthiazol-2-yl)hydrazine derivatives (5a-w) using an ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([Bmim]Br). The compounds were screened for their in vitro antimycobacterial activity against Mycobacterium tuberculosis. Compound 5s showed the highest inhibitory activity with an MIC of 6.03 μM which is slightly lower than the MIC values of standard drugs ethambutol (15.3 μM) and ciprofloxacin (9.4 μM). Four other compounds of the series viz.5e, 5i, 5t and 5w also showed significant inhibitory activity with MIC values in the range of 11.7-13.9 μM. The structure-activity relationship revealed that the trifluoromethyl substitution at position-2 and p-chlorophenyl substitution at position-6 of the imidazo[2,1-b][1,3,4]thiadiazole ring enhanced the inhibitory activity. Also, the methyl, methoxy, fluoro or nitro substituents on the thiazole ring enhanced the activity of the compounds. None of the active compounds were toxic to a normal cell line (NIH 3T3), which signifies the lack of general cellular toxicity of the molecules. In silico molecular docking studies revealed the favourable interaction of the potent compounds with the target enzymes InhA and CYP121.
- Ramprasad, Jurupula,Nayak, Nagabhushana,Dalimba, Udayakumar,Yogeeswari, Perumal,Sriram, Dharmarajan
-
p. 338 - 344
(2016/03/01)
-
- Synthesis, biological evaluation and molecular modeling study of thiadiazolo[3,2-a][1,3]diazepine analogues of HIE-124 as a new class of short acting hypnotics
-
A new series of 6,7-dihydro-[1,3,4]thiadiazolo[3,2-a][1,3]diazepine analogues were synthesized, and biological evaluated. Compound GS-62 (33) exhibited potent in?vivo short acting hypnotic activity with onset time, duration of sleep and therapeutic index of 6.4?±?0.2, 94.8?±?5.3?min, 6.62, respectively), in comparison to thiopental sodium (6). Compounds 33 did not show any sign of acute tolerance reported with the maintenance dose of 6. Meanwhile 33 potentiated the in?vivo hypnotic effect of 6 in an equimolar amounts (0.06?mmol) combination showing an onset and duration of 7.5?±?1.3, 62.5?±?5.9?min, respectively. This combination allowed the use of lower doses of both drugs to avoid the undesirable side effects. Docking studies revealed favorable interactions and binding to BDZ binding site of the GABAAreceptor especially with Arg87, Arg149, and Thr151 amino acid residues.
- El-Subbagh, Hussein I.,Hassan, Ghada S.,El-Taher, Kamal E.H.,El-Messery, Shahenda M.,El-Azab, Adel S.,Abdelaziz, Alaa A.-M.,Hefnawy, Mohamed M.
-
p. 237 - 247
(2016/09/09)
-
- Synthesis and antibacterial activities of thiadiazole maneb
-
Summary: Four novel maneb derivatives containing 1, 3, 4-thiadiazole were successfully synthesized and characterized by FT-IR, electrochemical analysis and 1H-NMR and 13C-NMR. And their antibacterial activities were screened for Paddy fusarium, Borrytis cinerea, Cucumber fusarium, Tomato gibberella, Grape white rot in vitro by filter paper disc diffusion technique. The target compounds exhibited moderate to excellent activity in comparison to maneb.
- Yuting, Liu,Gangtao, Liang,Dawei, Yin
-
p. 115 - 121
(2015/05/20)
-
- Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives
-
In this report, we describe the synthesis and biological evaluation of a new series of 2-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-1H-benzimidazole derivatives (5a-ac). The molecules were analyzed by 1H NMR, 13C NMR, mass spectral and elemental data. The structure of one of the pre-final compounds, 6-(4-methoxyphenyl)-2-(4-methylphenyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde (4d) and that of a target compound, 2-[2-methyl-6-(4-methyl phenyl) imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-1H-benzimidazole (5aa) were confirmed by single crystal XRD studies. All the target compounds were screened for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Seven (5c, 5d, 5l, 5p, 5r, 5z and 5aa) out of twenty nine compounds showed potent anti-tubercular activity with a MIC of 3.125 μg/mL. A p-substituted phenyl group (p-tolyl or p-chlorophenyl) in the imidazo[2,1-b][1,3,4]thiadiazole ring and/or a chloro group in the benzimidazole ring enhance anti-tuberculosis activity whereas a nitro group in the benzimidazole ring reduces the activity. In the antibacterial screening, compounds 5i, 5w and 5ac showed promising activity against the tested bacterial strains. Further, antifungal and antioxidant activities of these molecules were also investigated. In the cytotoxicity study, the active antitubercular compounds exhibited very low toxicity against a normal cell line.
- Ramprasad, Jurupula,Nayak, Nagabhushana,Dalimba, Udayakumar,Yogeeswari, Perumal,Sriram, Dharmarajan,Peethambar,Achur, Rajeshwara,Kumar, H. S. Santosh
-
-
- Fe3+-selective naked-eye 'off-on' fluorescent probe: Its crystal structure and imaging in living cells
-
Four novel rhodamine-active probes L1-L4 have been proposed and characterized as fluorescent chemosensors for Fe3+. An 'off-on' type fluorescent enhancement was observed, which was induced by the interactions between Fe3+ and the probe, proven to adopt a 1:1 binding stoichiometry. The recognition properties of the target compounds with metal ions have been investigated in methanol-water (1:1, v/v) solution by the fluorescence and ultraviolet spectrum. In addition, a plausible application of probes in the imaging of HepG2 (liver cells) under the condition of reoxygenation (95% air, 5% CO2) exposed to Fe3+ ions was also demonstrated.
- Meng, Wen-Fei,Yang, Mei-Pan,Li, Bo,Cheng, Zhao,Yang, Bing-Qin
-
p. 8577 - 8581
(2014/12/10)
-
- Mild and convenient one-pot synthesis of 2-amino-1,3,4-thiadiazoles using trimethylsilyl isothiocyanate (TMSNCS)
-
A novel and efficient one-pot method has been developed for the synthesis of 2-amino-1,3,4-thiadiazoles using various carboxylic acid hydrazides with trimethylsilyl isothiocyanate (TMSNCS). In situ preparation of various thiosemicarbazides by the reaction
- Guda, Dinneswara Reddy,Cho, Hyeon Mo,Lee, Myong Euy
-
p. 6813 - 6816
(2013/05/22)
-
- Virtual screening identification of nonfolate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase
-
Folate analogue inhibitors of Leishmania major pteridine reductase (PTR1) are potential antiparasitic drug candidates for combined therapy with dihydrofolate reductase (DHFR) inhibitors. To identify new molecules with specificity for PTR1, we carried out a virtual screening of the Available Chemicals Directory (ACD) database to select compounds that could interact with L. major PTR1 but not with human DHFR. Through two rounds of drug discovery, we successfully identified eighteen drug-like molecules with low micromolar affinities and high in vitro specificity profiles. Their efficacy against Leishmania species was studied in cultured cells of the promastigote stage, using the compounds both alone and in combination with 1 (pyrimethamine; 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine). Six compounds showed efficacy only in combination. In toxicity tests against human fibroblasts, several compounds showed low toxicity. One compound, 5c (riluzole; 6-(trifluoromethoxy)- 1,3-benzothiazol-2-ylamine), a known drug approved for CNS pathologies, was active in combination and is suitable for early preclinical evaluation of its potential for label extension as a PTR1 inhibitor and antiparasitic drug candidate.
- Ferrari, Stefania,Morandi, Federica,Motiejunas, Domantas,Nerini, Erika,Henrich, Stefan,Luciani, Rosaria,Venturelli, Alberto,Lazzari, Sandra,Calò, Samuele,Gupta, Shreedhara,Hannaert, Veronique,Michels, Paul A. M.,Wade, Rebecca C.,Costi, M. Paola
-
experimental part
p. 211 - 221
(2011/03/19)
-
- Synthesis of novel aryloxy propanoyl thiadiazoles as potential antihypertensive agents
-
2-Amino-5-aryl/alkyl-1,3,4-thiadiazoles 3a-e were synthesized from aliphatic and aromatic acids and thiosemicarbazide. These 2-amino-5-aryl/alkyl- 1,3,4-thiadiazoles 3a-e were condensed with 2-(naphthalenyloxymethyl) oxirane 4a-b to prepare some naphthalenyloxy-propanol amine derivatives 5a-j. These compounds were synthesized as potential antihypertensive agents.
- Samel, Amarish B.,Pai, Nandini R.
-
experimental part
p. 1327 - 1330
(2011/10/07)
-
- Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamides
-
A series of cyclopropanecarboxamide were prepared and tested for antifungal activity in vivo. The preliminary bioassays indicated that some compounds are comparable to the commercial fungicides. To further explore the comprehensive structure-activity relationship on the basis of fungicidal activity data, comparative molecular field analysis (CoMFA) was performed, and a statistically reliable model with good predictive power (r2 = 0.8, q2 = 0.516) was achieved. Based on the CoMFA, compound 7p was designed and synthesized, which was found to display a good antifungal activity (79.38%) as 7g and 7h.
- Liu, Xing-Hai,Shi, Yan-Xia,Ma, Yi,Zhang, Chuan-Yu,Dong, Wei-Li,Pan, Li,Wang, Bao-Lei,Li, Bao-Ju,Li, Zheng-Ming
-
scheme or table
p. 2782 - 2786
(2009/10/19)
-
- Sulfonylureas as dual acting agents - Synthesis and biological activity
-
2-Amino-5-aryl/alkyl-1,3,4-thiadiazoles 3a-e were used as intermediates in the synthesis of some 1,3-substituted urea derivatives 5a-o to evaluate their antidiabetic activity as well as antibacterial activity. The obtained compounds exhibited marginal activity against the animal models and the selected microorganisms.
- Chavan, Ameya A.,Pai, Nandini R.
-
p. 771 - 777
(2008/03/11)
-
- Phase transfer catalysts promoting the one-pot synthesis under ultrasonic irradiation and biological activity of n-(5-substituted-1,3,4-thiadiazole-2-yl)- N'-(5-methylisoxazoyl)-thiourea derivatives
-
Reaction of 2-amino-5-substitute-1,3,4-thiadiazoles with 5-methylisoxazoyl chloride and ammonium thiocyanate under the condition of solid-liquid phase-transfer catalysis using polyethylene glycol-600 (PEG-600) as the catalyst under ultrasonic irradiation yielded N-(5-substituted-1,3,4-thiadiazole-2-yl)- N'-(5-methylisoxazoyl)-thiourea derivatives 3a-1 in good-to-excellent yield. The chemical structure of all compounds was established by 1H NMR, FTIR, MS, and elemental analysis studies. Some of the compounds were investigated for fungicidal activity. The bioassay results indicated that some of these compounds exhibit moderate fungicidal activities.
- Xiaodong, Yang
-
p. 387 - 392
(2008/09/19)
-
- Some novel 2-methyl-3-(1′3′4′-thiadiazoyl)-4-(3H) quinazolinones with anticonvulsant and CNS depressant activity
-
A series comprising six novel 2-methyl-3-(1′3′4′- thiadiazoyl)-4(3H)quinazolinones have been synthesized by condensing different 2-amino-1,3,4-thiadiazoles with 2-methyl benzoxazin-2-one and evaluated for anticonvulsant and CNS depressant activity. Compound 5f exhibited both anticonvulsant and CNS depressant activity.
- Mishra, Pradeep,Jatav, Varsha,Kashaw
-
p. 1165 - 1170
(2008/02/07)
-
- Polymer-supported dichlorophosphate: A recoverable new reagent for synthesis of 2-amino-1,3,4-thiadiazoles
-
Poly(ethylene glycol) (PEG) supported dichlorophosphate was efficiently used as a recoverable new dehydration reagent for rapid synthesis of 2-amino-5-substituted-1,3,4-thiadiazoles under microwave irradiation and solvent-free condition by reactions of thiosemicarbazide with aliphatic acids, benzoic acid, aryloxyacetic acids or furan-2-carboxylic acids.
- Li, Zheng,Yu, Jin-Lan,Yang, Jing-Ya,Shi, Sheng-Yi,Wang, Xi-Cun
-
p. 341 - 343
(2007/10/03)
-
- Thiadiazolyl quinazolones as potential antiviral and antihypertensive agents
-
Phthalic anhydride on treatment with β-ethanol amine gives N-hydroxy ethyl phthalimide I which reacts with anthranilic acid in presence of ethanol containing concentrated hydrochloric acid affording 5-(N-ethylphthalimido)- anthranilic acid 2. This on treatment with benzoyl chloride in pyridine gives 6-(N-ethyl phthalimido)-2-phenyl-4-oxo-3, 4-dihydrobenzoxazine 3 which on reaction with 2-amino-5-aralkyl-1, 3, 4-thiadiazoles 4 in pyridine results in the formation of 6-(N-ethylphthalimido)-3-[2′-(5′-aralkyl-1′, 3′, 4′-thiadiazolyl)]-2-phenyl-4-oxo-(3H)-quinazolines 5. The antiviral and antihypertensive activities of 5 have been reported.
- Pandey,Tusi, Sarah,Tusi, Zehra,Raghubir,Dixit,Joshi,Bajpai
-
p. 180 - 183
(2007/10/03)
-
- Synthesis of thiadiazolo-s-triazines for their antiviral activity based on QSAR studies
-
2-Amino-5-aralkyl-1,3,4-thiadiazole 1 on treatment with benzaldehyde yields 5-aralkyl-2-benzylideno-imino-1,3,4-thiadiazole 2 which on reaction with ammonium thiocyanate cyclises to give 2-phenyl-7-aralkyl-1,3,4-thiadiazolo-[3,2-a]-s-triazine-5-[6H,7H]-thione 3. Reaction of 3 with p-toluene sulphonyl chloride in anhydrous chloroform gives 2-phenyl-3-(p-toluenesulphonyl)-7-aralkyl-1,3,4-thiadiazolo-[3, 2-al-s-triazine-5-[6H,7H]-thiones 4g-I. Benzoyl chloride also reacts with 3 in anhydrous pyridine giving 2-phenyl-3-(benzoyl)-7-aralkyl-1,3,4-thiadiazolo-[3,2-a]-s-triazine-5-[6H,7H] -thiones 4a-f in quantitative yields. The antiviral activities of 4 based on QSAR studies have been reported using physicochemical method.
- Pandey,Tusi,Tandon,Joshi,Bajpai
-
p. 2583 - 2588
(2007/10/03)
-
- Synthesis and biological activity of some new benzophenothiazines
-
Condensation of carboxylic acids with thiosemicarbazide in presence of conc. H2SO4 gives 2-amino-5-aralkyl-1,3,4-thiadiazoles 1 which on diazotization afford 5-aralkyl-1,3,4-thiadiazolyl-2-diazonium chlorides 2. Reaction of 2 with cold solution of β-naphthol in dilute NaOH furnishes α-(2-diazo-5-aralkyl-1,3,4-thiadiazolyl)-β-sodionaphthoxides 3 which on acidification with conc. HCl gives α-(2-diazo-5-aralkyl-1,3,4-thiadiazolyl)-β-naphthols 4. Reaction of 4 with p-anisidine gives α-(2-diazo-5-aralkyl-1,3,4-thiadiazolyl)-β-(p-anisidino) naphthalenes 5. Fusion of 5 with sulphur in presence of iodine results in 1-(2′-diazo-5′-aralkyl-1′,3′,4′- thiadiazolyl)-6-methoxy benzophenothiazines 6 in yields varying from 48% to 59%. The new compounds 6 have been screened for their antiviral and antifungal activities.
- Pandey,Negi,Joshi,Bajpai
-
p. 206 - 210
(2007/10/03)
-
- Synthesis of [1,3,4]thiadiazolo[3,2-a]pyrimidines in the presence of formic acid
-
Formic acid-phosphorus pentoxide was effective for the preparation of 5,7-dimethyl[1,3,4]thiadiazolo- and -[1,3]thiazolo[3,2-a]pyrimidin-4-ium salts. Further, the pyrimidine ring transformation and the isocyanation of 5imino-6H-[1,3,4]thiadiazolo- and -[1,3]thiazolo[3,2-a]pyrimidin-7-ones were carried out in the presence of formic acid and triethyl orthoformate, respectively.
- Takenaka, Keiko,Tsuji, Tadakazu
-
p. 1367 - 1370
(2007/10/03)
-
- Cyclization Reactions of Tricarbonylmethane Thiosemicarbazones: Formation of 1,3,4-Thiadiazole Derivatives with Concomitant C-C Bond Cleavage
-
Under acylating conditions 3-acetyl-4-hydroxy-2H-pyran-2-one thiosemicarbazones (1a, b and 2a, b) are transformed into 2-(acylamino)-5-methyl-1,3,4-thiadiazoles 3b, c, e, f and 2H-pyran-2-ones 1c and 2c via C-C bond cleavage.Similarly, the reaction of 1b with RCO2H/EtOH (R = Me, Et) affords 2-anilino-5-methyl-1,3,4-thiadiazole (3d) and triacetic acid lactone 1c.Upon treatment with Ac2O/Et3N the dehydroacetic acid derivative 1b is transformed into the thiadiazoline 4, while the benzo derivative 2b is converted into thiadiazole 3e and 4-acetoxycoumarin (2c). - Key Words: 2H-Pyran-2-ones / Coumarins / 1,3,4-Thiadiazoles / Thiosemicarbazones
- Somogyi, Laszlo
-
p. 721 - 724
(2007/10/02)
-
- CARBON TRANSFER REACTIONS OF Δ2-OXAZOLINIUM AND THIAZOLINIUM CATIONS
-
Δ2-Oxazolinium and thiazolinium cations with or without an appendage at any of the heteroatoms transfer their C(2) units at the carboxylic acid oxidation level to binucleophiles and provide the corresponding heterocycles, thus mimicking carbon transfer reactions exhibited by THF models, N-methyl N'-tosyl/acetyl imidazolinium cations.However, these azolinium cations react with phenethylamine and tryptamine to furnish their N-acyl derivatives.
- Singh, Harjit,Sarin, Rakesh
-
p. 1449 - 1460
(2007/10/02)
-
- Δ2-OXAZOLINIUM AND THIAZOLINIUM CATIONS AS ONE CARBON UNIT TRANSFER AGENTS
-
N-Methyl-Δ2-oxazolinium and thiazolinium cations tranfer their C2 units to binucleophiles in refluxing DMF or CH3CN and provide the corresponding heterocycles.
- Singh, Harjit,Sarin, Rakesh
-
p. 1101 - 1104
(2007/10/02)
-
- Derives de la dihydro-2,4 triazole-1,2,4 thione-3 et de l'amino-2 thiadiazole-1,3,4 a partir de nouvelles thiosemicarbazones d'esters
-
A new general synthesis of 4,5-disubstituted 2,4-dihydro-1,2,3-triazole-3-thiones is proposed.These heterocycles are obtained by the action of primary amines, aralhydrazines or aroylhydrazines on the thiosemicarbazones of esters.These last compounds are prepared by action of chlorhydrates of iminoesters on thiosemicarbazide in dimethylformamide.These thiosemicarbazones react also with strong acids, acid anhydrides and chlorides; by thermolysis and they give 2-amino-1,3,4-thiadiazole derivatives.Also, two derivatives of 1,2,4-triazolo-1,3,4-thiadiazole have been prepared.
- Malbec, Frederique,Milcent, Rene,Barbier, Geo
-
p. 1689 - 1698
(2007/10/02)
-
- Convenient Synthesis of 2,7-Disubstituted 5H-1,3,4-Thiadiazolopyrimidin-5-ones and Related Compounds
-
2,7-Disubstituted 5H-1,3,4-thiadiazolopyrimidin-5-ones were synthesized from the reaction of 3-amino-6-methyl-2-thiouracil with carboxylic acid or from that of thiosemicarbazide with carboxylic acid and β-keto ester in the presence of phosphorus pentaoxide and methanesulfonic acid.The synthesis of related compounds is also described.
- Tsuji, Tadakazu,Takenaka, Keiko
-
p. 637 - 638
(2007/10/02)
-
- Iminoisoindolinone metal complex
-
Iminoisoindolinone metal complexes of formula STR1 wherein A represents a 5- or 6-membered heterocyclic radical which contains at least one further heteroatom and can be fused or doubled with benzene nuclei, M represents a divalent metal atom excluding the alkaline earth metals, X represents a hydrogen atom, Y represents a halogen atom, Z represents a nitro group, an alkoxycarbonyl group of 2 to 6 carbon atoms or a group of formula RY2 --, wherein R represents a hydrogen atom, an alkyl group of 1 to 6 carbon atoms which is substituted by an aryl radical or is unsubstituted, a cycloalkyl group of 5 to 6 carbon atoms, or represents an aryl group, and Y2 represents an oxygen or a sulphur atom, m and n are 0 to 4, p is 0 to 2, and the sum of m+n+p must be 4, which are useful for pigmenting high molecular organic material.
- -
-
-