- Synthesis and Biological Evaluation of Oxadiazole Clubbed Thiadiazole Derivatives as Antimicrobial Agents
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A series of 1,3,4-oxadiazole clubbed 1,3,4-thiadiazole derivatives were synthesized and assessed in vitro for their activity as antimicrobial agents. The target compounds 2-(5-(substituted aryl)-1, 3, 4-oxadiazol-2-ylthio)-N-(5-(substituted aryl)-1, 3, 4-thiadiazol-2-yl) acetamides (5a-5s) were synthesized using a basic condensation reaction between 5-(substituted aryl)-1,3,4-oxadiazole-2-thiol and 2-chloro-N-(5-(substituted aryl)-1,3,4-thiadiazol-2-yl)acetamide in presence of K2CO3 as a scavenging agent and acetone as reaction solvent. The titled compounds synthesized here, exhibited excellent to moderate antimicrobial activity against a broad panel of antibacterial strains of Gram-positive and Gram-negative bacteria and fungi.
- Begari, Eeshwaraiah,Dave, Alpa Y.,Joshi, Deepkumar S.,Parmar, Kokila A.
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p. 273 - 280
(2021/08/03)
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- 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
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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.
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- Benzoxazole/benzothiazole-derived VEGFR-2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations
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A novel series of benzoxazole/benzothiazole derivatives 4a–c–11a–e were designed, synthesized, and evaluated for anticancer activity against HepG2, HCT-116, and MCF-7 cells. HCT-116 was the most sensitive cell line to the influence of the new derivatives. In particular, compound 4c was found to be the most potent derivative against HepG2, HCT-116, and MCF-7 cells, with IC50 values = 9.45 ± 0.8, 5.76 ± 0.4, and 7.36 ± 0.5 μM, respectively. Compounds 4b, 9f, and 9c showed the highest anticancer activities against HepG2 cells with IC50 values of 9.97 ± 0.8, 9.99 ± 0.8, and 11.02 ± 1.0 μM, respectively, HCT-116 cells with IC50 values of 6.99 ± 0.5, 7.44 ± 0.4, and 8.15 ± 0.8 μM, respectively, and MCF-7 cells with IC50 values of 7.89 ± 0.7, 8.24 ± 0.7, and 9.32 ± 0.7 μM, respectively, in comparison with sorafenib as reference drug with IC50 values of 9.18 ± 0.6, 5.47 ± 0.3, and 7.26 ± 0.3 μM, respectively. The most active compounds 4a–c, 9b,c,e,f,h, and 11c,e were further evaluated for their VEGFR-2 inhibition. Compounds 4c and 4b potently inhibited VEGFR-2 at IC50 values of 0.12 ± 0.01 and 0.13 ± 0.02 μM, respectively, which are nearly equipotent to the sorafenib IC50 value (0.10 ± 0.02 μM). Furthermore, molecular docking studies were performed for all synthesized compounds to assess their binding pattern and affinity toward the VEGFR-2 active site.
- El-Helby, Abdel-Ghany A.,Sakr, Helmy,Eissa, Ibrahim H.,Al-Karmalawy, Ahmed A.,El-Adl, Khaled
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- Phenyl substituted thiadiazole thiazolinone compound, preparation method and application thereof
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The invention discloses a phenyl substituted thiadiazole thiazolinone compound. A chemical construction thereof is shown as following formula. According to the invention, the phenyl substituted thiadiazole thiazolinone compound is prepared according the f
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- COMPOUNDS FOR MODULATING AQUAPORINS
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The invention relates to compounds of formula (I) pharmaceutical compositions thereof and methods for modulating aquaporin 9.
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Page/Page column 39; 43-44
(2017/12/08)
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- Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure-Activity Relationship Study
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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
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p. 1599 - 1612
(2016/03/05)
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- Design of benzothiazole-1,3,4-thiadiazole conjugates: Synthesis and anticonvulsant evaluation
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Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted- phenyl-1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity. Their quantitative study indicated an increase of nearly 2-10 times for the MES test and 7- to 67-fold for the scPTZ test in the protective index, the keystone in drug discovery for anticonvulsant activity. Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl-1,3, 4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. Three potent candidates (5i, 5t, and 5u) with minimal neurotoxicity were identified in the MES and scPTZ tests.
- Siddiqui, Nadeem,Ahuja, Priya,Malik, Sachin,Arya, Satish K.
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p. 819 - 831
(2013/12/04)
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- Synthesis and antifungal activity of thiadiazole-functionalized chitosan derivatives
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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
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p. 103 - 107
(2013/06/27)
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- Thiadiazole derivatives as potential anticonvulsant agents
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A series of thiadiazole derivatives were synthesized with differently substituted benzoic acids which were cyclized to give differently substituted thiazolidin-4-one. Elemental analysis, IR,1HNMR,13C NMR and mass spectral data confir
- Mullick, Pooja,Khan, Suroor A.,Verma, Surajpal,Alam, Ozair
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p. 1011 - 1016
(2012/01/03)
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- Synthesis and evaluation of some 2-[(substituted) ethanoyl]amino- 5-aryl-1,3,4-thiadiazoles as diuretic agents
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Twelve 2-[(substituted)ethanoyl]amino-5-aryl-1,3,4-thiadiazoles were prepared by the reaction of 2-(chloro ethanoyl)amino-5-aryl-1,3,4- thiadiazoles and various secondary amines. These compounds were screened for diuretic activity. The compounds namely 4a1, 4b2 and 4c2 showed good diuretic activity comparable with the standard drug acetazolamide at a dose level of 100 mg/kg, orally in albino rats.
- Jain, Sanmati K.,Mishra, Pradeep
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p. 1305 - 1308
(2011/12/21)
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- Synthesis, characterization and antimicrobial activity of new thiadiazole derivatives
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A series of thiadiazole derivatives were synthesized with differently substituted benzoic acids which were cyclized to give differently substituted thiazolidin-4-one. Elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data confirmed the
- Mullick, Pooja,Khan, Suroor A.,Verma, Surajpal,Alam, Ozair
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experimental part
p. 2345 - 2350
(2010/11/16)
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- THIENOPYRIDINE DERIVATIVES FOR THE TREATMENT AND PREVENTION OF DENGUE VIRUS INFECTIONS
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Methods and pharmaceutical compositions for treating viral infections, by administering certain thienopyridine derivative compounds in therapeutically effective amounts are disclosed. Methods of using the compounds and pharmaceutical compositions thereof are also disclosed. In particular, the treatment and prophylaxis of viral infections such as caused by flavivirus is disclosed, i.e., including but not limited to, Dengue virus, West Nile virus, yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus.
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Page/Page column 94-95
(2010/09/17)
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- Synthesis of 2-(5-substituted-1,3,4-thiadiazolo-2-ylimino)-4- thiazolidinones under microwave irradiation
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Fifteen 2-(5-substituted-1,3,4-thiadiazolo-2-ylimino)-4-thiazolidinones were efficiently synthesized from the reaction of ammonium thiocyanate with 2-chloro-N-(5-substutited-1,3,4-thiadiazolo-2-yl)acetamides under microwave irradiation. The target compoun
- Wang, Xi-Cun,Huang, Guo-Li,Quan, Zheng-Jun,Lv, Cheng-Wei,Yang, Wen-Long
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p. 973 - 982
(2008/09/17)
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- Preparation and evaluation of some 1,3,4-thiadiazoles as diuretic agents
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Sixteen newer 2-(substituted acetamido)-5-aryl-1,3,4-thiadiazoles have been prepared and screened for LD50 and diuretic activity. A few of the compounds namely 4.1, 4.2 and 40 shows diuretic activity comparable with the standard drug acetazolam
- Jain, Sanmati K.,Mishra
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p. 184 - 188
(2007/10/03)
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