- Synthesis of a Series of Novel 2-Amino-5-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole Derivatives as Potential Anticancer, Antifungal and Anti-bacterial Agents
-
Objective: The objective of the present study was to prepare the 5-substituted 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole derivatives and evaluate their potential anticancer, antibac-terial and antifungal activities. Methods: Twenty-seven derivatives were synthesized by iodine-mediated cyclization of semicarba-zones or thiosemicarbazones obtained from condensation of semicarbazide or thiosemicarbazide and aldehydes. The structures were confirmed by1H-NMR,13C-NMR and MS spectra. The antibacterial and antifungal activities were evaluated by diffusion method and the anticancer activities were evaluated by MTT assay. Results: Twenty-seven derivatives have been synthesized in moderate to good yields. A number of derivatives exhibited potential antibacterial, antifungal and anticancer activities. Conclusion: Compounds (1b, 1e and 1g) showed antibacterial activity against Streptococcus faecal-is, MSSA and MRSA with MIC value ranging between 4 to 64 μg/mL. Compound (2g) showed anti-fungal activity against Candida albicans (8 μg/mL) and Aspergillus niger (64 μg/mL). Compound (1o) exhibited high cytotoxic activity against HepG2 cell line (IC50 value 8.6 μM) which is compara-ble to the activity of paclitaxel, and is non-toxic on LLC-PK1 normal cell line. The structure activity relationship and molecular docking study of the synthesized compounds have also been reported.
- Do, tuoi thi Hong,Dong, Nguyen Hanh,Vo, Duy Duc,pham, Em canh,truong, tuyen Ngoc
-
p. 558 - 573
(2022/03/09)
-
- HERBICIDAL COMPOUNDS
-
Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially as herbicides.
- -
-
Page/Page column 75
(2021/04/10)
-
- Aryl or heteroaryl substituted thiadiazole compound and antibacterial application thereof
-
The invention belongs to the technical field of medicines, and particularly relates to an aryl or heteroaryl substituted thiadiazole compound, a preparation method and application thereof as an antibacterial drug. The compound is represented by formula (1
- -
-
Paragraph 0095-0097; 0194-0195
(2021/01/30)
-
- 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 0045-0051
(2020/02/14)
-
- Novel fatty acid-thiadiazole derivatives as potential antimycobacterial agents
-
The discovery of antibiotics around the middle twentieth century led to a decrease in the interest in antimycobacterial fatty acids. In order to re-establish the importance of naturally abundant fatty acid, a series of fatty acid-thiadiazole derivatives were designed and synthesized based on molecular hybridization approach. In vitro antimycobacterial potential was established by a screening of synthesized compounds against Mycobacterium tuberculosis H37Rv strain. Among them, compounds 5a, 5d, 5h, and 5j were the most active, with compound 5j exhibiting minimum inhibitory concentration of 2.34?μg/ml against M.tb H37Rv. Additionally, the compounds were docked to determine the probable binding interactions and understand the mechanism of action of most active molecules on enoyl-acyl carrier protein reductases (InhA), which is involved in the mycobacterium fatty acid biosynthetic pathway.
- Mali, Jaishree K.,Sutar, Yogesh B.,Pahelkar, Akshata R.,Verma, Preeti M.,Telvekar, Vikas N.
-
p. 174 - 181
(2019/11/03)
-
- 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
-
-
- Pyridine and nitro-phenyl linked 1,3,4-thiadiazoles as MDR-TB inhibitors
-
In the present study, a series of substituted 1,3,4-thiadiazole derivatives 4(a–o), 5(a–m) and 6(a–j) were synthesized and characterized by IR, 1H NMR, 13C NMR and mass spectroscopic technique. The synthesized compounds were evaluate
- Patel, Harun,Jadhav, Harsha,Ansari, Iqrar,Pawara, Rahul,Surana, Sanjay
-
-
- Thiadiazolodiazepine analogues as a new class of neuromuscular blocking agents: Synthesis, biological evaluation and molecular modeling study
-
The synthesis, biological evaluation and molecular modeling study of 6,7-dihydro-[1,3,4] thiadiazolo[3,2-a][1,3]diazepine analogues as new class of neuromuscular blocking agents are described. The new compounds act via competitive mechanism with ACh which
- El-Subbagh, Hussein I.,El-Azab, Adel S.,Hassan, Ghada S.,El-Messery, Shahenda M.,Abdel-Aziz, Alaa A.-M.,El-Taher, Kamal E.H.
-
-
- 2-(4-pyridyl)-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method
-
The present invention discloses a 2-(4-pyridyl)-6-ferrocenyl-imidazo[2,1-b]-1,3,4-thiadiazole preparation method, which comprises: carrying out stirring mixing on 2-amino-5-(4-pyridyl)-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 0025; 0029; 0030; 0040; 0051
(2018/01/12)
-
- Natural product-inspired rational design, synthesis and biological evaluation of 2,3-dihydropyrano[2,3-f]chromen-4(8H)-one based hybrids as potential mitochondrial apoptosis inducers
-
Synthesis of novel pyranochromanone amide hybrids, by combining pyranochromanone pharmacophore and privileged scaffolds such as 2-amino-1,3,4-thiadiaole/2-aminothiazole/aminopyridine/aminonaphthalene and anti-cancer evaluation of a series led us to discover a series of new chemical entities (NCEs) showing broad spectrum of anti-cancer activity against three different human cancer cell lines (MCF-7, A549 and HeLa), at IC50values ranging from 14.3 to 97.8?μM. Among them, some compounds such as 15b, 15d, 20a and 20b displayed excellent activity against breast cancer cell line MCF-7. Detailed biological studies such as AO/EB dual staining, Hoechst 33342 staining, FACS analysis of mitochondrial membrane potential (Δψm) using JC-1 dye and DNA fragmentation confirmed the apoptosis induced by the hybrids. Gene expression studies by Real time RT-PCR has shown that these compounds are efficient regulator of anti-apoptotic gene Bcl-2. Western blot analysis also revealed that these compounds persuade apoptosis through intrinsic pathway by up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Molecular docking studies reveal that compounds 15b and 20b binds efficiently with Bcl-2 promoter G-quadruplex.
- Sakthivel, Palaniappan,Ilangovan, Andivelu,Kaushik, Mahabir Prasad
-
p. 302 - 318
(2016/07/11)
-
- 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents: Synthesis, bioevaluation and docking study
-
The search for newer histone deacetylase (HDAC) inhibitors has attracted a great deal of interest of medicinal chemists worldwide, especially after the first HDAC inhibitor (Zolinza , widely known as SAHA or Suberoylanilide hydroxamic acid) was approved by the FDA for the treatment of Tcell lymphoma in 2006. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. Most of the compounds in this series, e.g. compounds with 5-aryl moiety being 2-furfuryl (5a), 5-bromofuran-2-yl (5b), 5-methylfuran-2-yl (5c), thiophen-2-yl (5d), 5-methylthiophen-2-yl (5f) and pyridyl (5g-i), were found to have potent anticancer cytotoxicity with IC50 values of generally 5-to 10-fold lower than that of SAHA in 4 human cancer cell lines assayed. Those compounds with potent cytotoxicity were also found to have strong HDAC inhibition effects. Docking studies revealed that compounds 5a and 5d displayed high affinities towards HDAC2 and 8.
- Huong, Tran Thi Lan,Dung, Do Thi Mai,Oanh, Dao Thi Kim,Lan, Tran Thi Bich,Dung, Phan Thi Phuong,Loi, Vu Duc,Kim, Kyung Rok,Han, Byung Woo,Yun, Jieun,Kang, Jong Soon,Kim, Youngsoo,Han, Sang-Bae,Nam, Nguyen-Hai
-
p. 296 - 304
(2016/03/22)
-
- Improved antiproliferative activity of 1,3,4-thiadiazole-containing histone deacetylase (HDAC) inhibitors by introduction of the heteroaromatic surface recognition motif
-
A series of 1,3,4-thiadiazole-containing hydroxamic acids, in accord with the common pharmacophore of histone deacetylase (HDAC) inhibitors (a Zn2+ binding moiety-a linker-a surface recognition motif), was identified as submicromolar HDAC inhibitors by our group. In this study, we continued our efforts to develop 1,3,4-thiadiazole bearing hydroxamate analogues by modifying the surface recognition motif. We found that 1,3,4-thiadiazoles having a heteroaromatic substituent showed better HDAC inhibitory activity in enzymatic assay and higher antiproliferative potency in cellular assay compared to SAHA.
- Guan, Peng,Wang, Lei,Hou, Xuben,Wan, Yichao,Xu, Wenfang,Tang, Weiping,Fang, Hao
-
p. 5766 - 5775
(2015/02/02)
-
- 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)
-
- CYTOSINE DEAMINASE MODULATORS FOR ENHANCEMENT OF DNA TRANSFECTION
-
Compounds and methods are provided for enhancing or boosting the transfection rate or efficiency of mammalian cells by foreign DNA, such as bacterial plasmid DNA. Compounds, including natural products and inventive synthetic compounds can increase the effectiveness of uptake and incorporation of foreign DNA by mammalian cells, such as human cells, by suppression of DNA cytosine deamination, which is believed to be a mechanism by which these cells eliminate foreign DNA. Inhibition of the cytosine deaminase enzymes by compounds as described herein serves to provide more effective transfection of eukaryotic cells by plasmids including engineered gene sequences. Transfection can be used to study cellular processes, or to cure genetic diseases in human patients. The inventive materials and methods increase the efficiency and effectiveness of such transfection techniques.
- -
-
Page/Page column 67
(2013/06/05)
-
- Phenylalanine derivatives as GPR142 agonists for the treatment of Type II diabetes
-
GPR142 is a novel GPCR that is predominantly expressed in pancreatic β-cells. GPR142 agonists potentiate glucose-dependent insulin secretion, and therefore can reduce the risk of hypoglycemia. Optimization of our lead pyridinone-phenylalanine series led to a proof-of-concept compound 22, which showed in vivo efficacy in mice with dose-dependent increase in insulin secretion and a decrease in glucose levels.
- Du, Xiaohui,Kim, Yong-Jae,Lai, Sujen,Chen, Xi,Lizarzaburu, Mike,Turcotte, Simon,Fu, Zice,Liu, Qingxiang,Zhang, Ying,Motani, Alykhan,Oda, Kozo,Okuyama, Ryo,Nara, Futoshi,Murakoshi, Michiko,Fu, Angela,Reagan, Jeff D.,Fan, Peter,Xiong, Yumei,Shen, Wang,Li, Leping,Houze, Jonathan,Medina, Julio C.
-
p. 6218 - 6223
(2012/10/29)
-
- Calix[4]arene based 1,3,4-oxadiazole and thiadiazole derivatives: Design, synthesis, and biological evaluation
-
In the present investigation, we describe some novel calixarene based heterocyclic compounds (5a-5i) in which 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives have been coupled with 5,11,17,23-tetra-tert-butyl-25,27- bis(chlorocarbonyl-methoxy)-26,28-dihydroxy calix[4]arene. All the newly synthesized calixarene based heterocyclic compounds have been characterized by elemental analysis and various spectroscopic methods like FTIR, 1H NMR, 13C NMR, and FAB-MS. All the final scaffolds have been subjected to antioxidant activity, in vitro antimicrobial screening against two gram (+ve) bacteria (S. aureus, S. pyogenes), two gram (-ve) bacteria (E. coli, P. aeruginosa) and two fungal strains (C. albicans, A. clavatus) and also have been screened for their antitubercular activity against Mycobacterium tuberculosis H37Rv.
- Patel, Manishkumar B.,Modi, Nishith R.,Raval, Jignesh P.,Menon, Shobhana K.
-
experimental part
p. 1785 - 1794
(2012/04/23)
-
- Synthesis, insecticidal evaluation of novel 1,3,4-thiadiazole chrysanthemamide derivatives formed by an EDCI/HOBt condensation
-
A series of novel pesticides with two components derived from a 1,3,4-thiadiazole and chrysanthemic acid were synthesised via an EDCI/HOBt condensation. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, 1H NMR and elemental analyses. Their insecticidal activity was also evaluated.
- Yu, Peng,Hu, Jun,Zhou, Tao-Yu,Wang, Peng,Xu, Yan-Hua
-
experimental part
p. 703 - 706
(2012/03/10)
-
- Synthesis and insecticidal activities of novel 1,3,4-thiadiazole 5-fluorouracil acetamides derivatives: An RNA interference insecticide
-
A series of novel 1,3,4-thiadiazole 5-fluorouracil acetamides derivatives were designed and synthesized. Their structures were confirmed by infrared, 1H NMR spectroscopy, and elemental analysis. The insecticidal activities against Tetranychus cinnabarinus
- Wan, Rong,Zhang, Jian-Qiang,Han, Fen,Wang, Peng,Yu, Peng,He, Qiu
-
experimental part
p. 280 - 292
(2012/02/03)
-
- Synthesis, crystal structure and bioactivities of N-(2,6-difluorobenzoyl)- N′-[5-(pyrid-4-yl)-1,3,4-thiadiazol-2-yl]urea
-
N-(2,6-difluorobenzoyl)-N′-[5-(pyrid-4-yl)-1,3,4-thiadiazol-2-yl] urea, 3, has been synthesized by reaction of 2-amino-5-(pyrid-4-yl)-1,3,4- thiadiazole with 2,6-difluorobenzoyl isocyanate, and its structure was characterized with X-ray crystallographic,
- Song, Xin-Jian,Tan, Xiao-Hong,Wang, Yan-Gang
-
p. 479 - 482
(2008/09/20)
-
- COMPOSITIONS USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
-
The present invention relates to substitute thiazole and thiophene derivatives useful as inhibitors of rock and other protein kinaeses. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders, including proliferative, cardiac and neurodegenerative diseases.
- -
-
Page 102-103
(2010/02/07)
-
- N-(1,3,4-thiadiazol-2-yl)benzamides
-
A series of N-(1,3,4-thiadiazol-2-yl)benzamides, having a phenyl, naphthyl or hetero-aryl group at the 5-position of the thiadiazole ring and 2,6-substitution on the benzamide ring, are useful insecticides. The invention also provides insecticidal methods
- -
-
-