- Insights into the nature of weak noncovalent interactions in 3-(4-fluorophenyl)-6-(2-fluorophenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole, a potential bioactive agent: X-ray, QTAIM and molecular docking analysis
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A thorough examination of weak interactions present in the crystal structure of the title compound was investigated. Intramolecular C–H?N and F?S interactions make the molecule as fused 6,5,5,5,6,6-membered ring system. Two of the closely related structur
- Al-Wahaibi, Lamya H.,Akilandeswari, Gopalan,Anusha, Ravisankar,Al-Shaalan, Nora H.,Alkmali, Omkulthom M.,El-Emam, Ali A.,Percino, Judith M.,Thamotharan, Subbiah
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- Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
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Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
- Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
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- Synthesis and antitumor evaluation of novel fused heterocyclic 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives
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In this study, twenty three 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives were synthesized and their antiproliferative activities in vitro were studied against SMMC-7721, HeLa, A549, and L929 by the CCK-8 assay. The bioassay results demonstrated that all tested compounds 8(a–w) exhibited antiproliferation with different degrees, and some compounds showed better effects than reference drug 5-fluorouracil. Among these screened compounds, compounds 8a, 8d, and 8l displayed significant antitumor activities in inhibiting SMMC-7721cell proliferation with IC50 values of 1.64, 1.74, and 1.61 μM, respectively. Compounds 8d and 8l were manifested highly effective biological activity versus HeLa cells with IC50 values of 2.23 and 2.84 μM, respectively. Compound 8l was found to have the highest antitumor potency against A549 cells with IC50 value of 2.67 μM. Furthermore, all compounds exhibited weaker cytotoxic effects than 5-fluorouracil on normal cell lines L929.
- Liu, Xiao-Jia,Liu, Hai-Ying,Wang, Hai-Xin,Shi, Yan-Ping,Tang, Rui,Zhang, Shuai,Chen, Bao-Quan
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p. 1718 - 1725
(2019/08/02)
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- Design, Synthesis and Evaluation of Antitubercular Activity of Novel 1,2,4-Triazoles Against MDR Strain of Mycobacterium tuberculosis
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Emergence of various forms of resistant strains of Mycobacterium tuberculosis led to the exploration of drugs with novel mechanism of action. Recently econazole, an azole based antitubercular agent, attracted major attention for targeting mycobacterial cytochrome P450. In the present study, we designed novel 1,2,4-triazole derivatives based on econazole moiety and evaluated them for in vitro antitubercular activity against M. tuberculosis H37Rv and multi-drug resistant (MDR) strains of Mycobacterium.
- Ganesh Kumar,Gautham Shenoy,Kar, Sidhartha Sankar,Shenoy, Vishnu,Bairy, Indira
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p. 907 - 917
(2018/02/07)
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- Synthesis and biological activities of cyclanone O-(2-(3-aryl-4- amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives
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Twelve cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives were synthesized and their structures were confirmed by spectroscopy (IR, 1H NMR, 13C NMR, 19F NMR) and elemental analysis. Their antifungal and antibacterial activities were evaluated against six fungi (Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora infestans, Paralepetopsis sasakii, Sclerotinia sclerotiorum) and two bacteria (Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas citri subsp. Citri (Xcc)). The results indicated that most of the title compounds exhibited good antibacterial activities. Among them, compounds 6d, 6g, 6h, and 6j showed better antibacterial activities against Xoo and Xcc than that of the commercial agent thiodiazole-copper.
- Chen, Meihang,Chen, Lijuan,Zhu, Xuesong,Wang, Xiaobin,Li, Qin,Zhang, Juping,Lu, Daowang,Xue, Wei
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p. 1259 - 1263
(2017/10/18)
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- Synthesis and biological activities of 3,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivatives
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Twelve novel triazolothiadiazole derivatives were synthesized from 4-amino-5-substituted-4H-1,2,4-triazole-3-thiols with various aromatic carboxylic acids by cyclization in the presence of phosphorous oxychloride. All the newly synthesized compounds were characterized by FTIR, 1H NMR, mass spectroscopy and elemental analysis. The antimicrobial activities of the title compounds were examined by disc diffusion method against Escherichia coli, Staphylococcus aureus, Pyricularia oryzae and Rhizoctnia solani. The bioassay indicated all synthesized triazolothiadiazole derivatives possessed moderate to good antibacterial and antifungal activities against the tested organisms. Especially, compounds 2e and 2k exhibited excellent antibacterial and antifungal activities among these triazolothiadiazole derivatives.
- Lin, Lu,Liu, Hua,Wang, Dun-Jia,Hu, Yan-Jun,Wei, Xian-Hong
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p. 481 - 489
(2018/02/06)
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- 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole compound and application thereof
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The invention discloses a group of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole compounds, and application thereof, namely application of ten 3-substituted phenyl-6-butyl dithio-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole compounds comprising 3-phenyl-6-n-butyl dithio-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole, 3-phenyl-6-isobutyl dithio-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole, 3-p-methoxyphenyl-6-n-butyl dithio-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and the like. The ten compounds have antitumor activity, are used for preparing drugs for fighting against cervical cancer (Hela), liver cancer (SMMC-7721) and lung cancer (A549), and create a new way for developing a new cancer-fighting drug.
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Paragraph 0081
(2017/07/22)
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- Synthesis and antibacterial activity of oxime ester derivatives containing 1,2,4-triazole or 1,3,4-oxadiazole moiety
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A series of oxime ester derivatives containing 1,2,4-triazole or 1,3,4-oxadiazole moiety were designed and synthesized, and their antibacterial activities in vitro against Xanthomonas axonopodis pv. citri (Xac) and Xanthomonas oryzae pv. oryzae (Xoo) were
- Wang, Xiaobin,Zhong, Xinmin,Zhu, Xuesong,Wang, Hua,Li, Qin,Zhang, Juping,Ruan, Xianghui,Xue, Wei
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p. 1953 - 1960
(2017/09/30)
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- SAR studies on 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles as inhibitors of Mtb shikimate dehydrogenase for the development of novel antitubercular agents
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Shikimate dehydrogenase, an essential protein for the biosynthesis of the chorismate end product, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of one lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole (1), targeting Mt SD in our previous study, an extensive SAR study for optimization of the lead compound was performed through systematic modification of the 3 and 6 positions. This study has successfully led to the discovery of two highly potent advanced leads 6d-4, 6c-4 and several other compounds with comparable potencies (6d-4, MIC-H37Rv = 0.5 μg mL-1; MIC-MDRTB = 4.0 μg mL-1; MIC-RDRTB = 0.5 μg mL-1; Mt SD-IC50 = 14.20 μg mL-1; and 6c-4, MIC-H37Rv = 0.5 μg mL-1; MIC-MDRTB = 4.0 μg mL-1; MIC-RDRTB = 1.0 μg mL-1; Mt SD-IC50 = 6.82 μg mL-1). These advanced lead compounds possess a para-halogen phenyl at the 3 position. In vitro Mt SD inhibitory assay indicates that Mt SD is the target for their antitubercular activity. Moreover, the BacT/ALERT 3D liquid culture technology and in vitro Mt SD inhibitory assay were initially applied.
- Li, Ziqiang,Liu, Yishuang,Bai, Xiaoguang,Deng, Qi,Wang, Juxian,Zhang, Guoning,Xiao, Chunling,Mei, Yaning,Wang, Yucheng
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p. 97089 - 97101
(2015/12/01)
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- Synthesis, anti-HIV activity and Molecular modeling study of 3-aryl-6-adamantylmethyl-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazole derivatives
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A series of novel 3-aryl-6-adamantylmethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 6a-l were synthesized by a simple method with the aim of developing novel HIV non-nucleoside reverse transcriptase inhibitors. All the synthesized compounds were structurally confirmed by spectral analyses. The structure of 6a was unambiguously verified by X-ray structure determination. The synthesized compounds were evaluated for their anti-HIV activity and four analogs displayed moderate inhibitory activity with EC50 values ranging from 10.10 to 12.40 μg mL-1. Molecular docking of 6g with HIV-1 reverse transcriptase was studied to rationalize some structureactivity relationships (SARs).
- Khan, Mahmood-Ul-Hassan,Hameed, Shahid,Farman, Muhammad,Al-Masoudia, Najim A.,Stoeckli-Evans, Helen
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p. 609 - 616
(2016/02/18)
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- Synthesis and antimicrobial evaluation of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety
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Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 μg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 μg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 μg/ml. All of the compounds synthesized in the current Letter were characterized by 1H NMR, 13C NMR, infrared and mass spectroscopy.
- Li, Chao,Liu, Jia-Chun,Li, Ya-Ru,Gou, Cheng,Zhang, Mei-Ling,Liu, Hong-Yan,Li, Xiao-Zhen,Zheng, Chang-Ji,Piao, Hu-Ri
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p. 3052 - 3056
(2015/06/22)
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- Synthesis, characterization and antimicrobial activities of mercaptoxadiazoles, mercaptotriazoles and their derivatives
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Five member heterocycles are famous for their universal activities. Starting with suitably substituted hydrazides 1,3,4-oxadiazole-2-thiones (1-5) and 1,2,4-triazolethionamines (6-11) were synthesized which were later on converted into Mannich products (13-22) and traizolothiadiazines (23-28) respectively. Structures were established by FTIR, hydrogen, carbon NMR, and mass spectrometric analysis. Compounds were evaluated for their antimicrobial studies. Compounds 13, 19 and 23 showed maximum inhibitions in opposition to the bacterial strains while compounds 7, 11, 13 and 27 showed utmost percentage inhibition aligned with the yeast cells.
- Mumtaz, Amara,Saeed, Aamer,Malik, Imran
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p. 852 - 857
(2015/01/30)
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- Microwave-assisted synthesis and in vitro antibacterial activity of novel steroidal 1,2,4-triazole Schiff base derivatives
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A series of novel Schiff bases containing both a 1,2,4-triazole and deoxycholic acid skeleton have been synthesised in excellent yields and in high purity by means of microwave irradiation. The structures of the target compounds were characterised by MS, IR and NMR as well as elemental analysis. All the products were evaluated for their in vitro antibacterial activities against Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative bacteria (Pseudomonas seruginosa and Escherichia coli). Four of the compounds displayed varying levels of antibacterial activity against P. aeruginosa and S. aureus, but none of the compounds showed any activity against E. coli and B. subtilis.
- Wang, Xiaohong,Liu, Xingli,Jiang, Yujia,Zhao, Zhigang
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p. 300 - 303
(2014/06/09)
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- METHODS FOR MODULATING PLANT RESPONSE TO ENVIRONMENTALLY-INDUCED STRESS
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Compounds and methods are described herein that are effective to modulate plant response (e.g., plant susceptibility) to environmentally-induced stress. The compounds and methods described herein advantageously may be used to modulate environmental stress
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Paragraph 0069; 0070
(2013/10/22)
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- Synthesis, characterization and fungicidal activities of novel fluorinated 3,5-disubstituted-4H-1,2,4-triazol-4-amines
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Thiocarbohydrazide and substituted benzoyl hydrazine were used as starting materials to synthesize fifteen fluorinated 3,5-disubstituted-4H-1,2,4-triazol- 4-amines. All the title compounds were characterized using IR, 1H and 19F NMR
- Chen, Min,Wang, Xian-Feng,Wang, Si-Si,Feng, Yi-Xiao,Chen, Feng,Yang, Chun-Long
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experimental part
p. 323 - 329
(2012/04/04)
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- A novel 5-mercapto triazole Schiff base as a selective chromogenic chemosensor for Cu2+
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A novel colorimetric cation sensor bearing phenol, thiol and HCN groups was designed and synthesized. In a DMSO/H2O (9:1, v/v) solution, the sensor exhibited highly selective recognition of Cu2+ among a range of metal ions tested. In the presence of Cu2+, solutions of the sensor underwent a dramatic color change from colorless to yellow, while the presence of other metal cations such as Zn2+, Pb2+, Cd2+, Ni2+, Co2+, Fe3+, Hg 2+, Ag+ and Ca2+ had no effect on the color. The detection limit of the sensor toward Cu2+ is 8.0 × 10 -7 M and an association constant Ka of 4.3 × 10 5 M-1 was measured. The sensing of Cu2+ by this sensor was found to be reversible, with the Cu2+-induced color being lost upon addition of EDTA.
- Liu, Ming-Xia,Wei, Tai-Bao,Lin, Qi,Zhang, You-Ming
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experimental part
p. 1837 - 1842
(2011/10/03)
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- Synthesis, crystal structure and antiproliferative activity of 6-adamantyl-3-aryl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles
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A series of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a - l bearing an adamantyl moiety were synthesized by condensation of 4-amino-5-aryl-2H-1,2,4-triazole-3(4H)-thiones 4a - l with adamantyl-1- carboxylic acid in the presence of POCl3. The structures of the newly synthesized compounds were established using spectroanalytical techniques and verified further by the crystal structure determination of compounds 5a and 5j. The compounds were screened for their antiproliferative activity against a large panel of human cell lines.
- Khan, Mahmood-Ul-Hassan,Akhtar, Tashfeen,Yasin, Khawaja A.,Al-Masoudi, Najim A.,Jones, Peter G.,Hameed, Shahid
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scheme or table
p. 178 - 184
(2010/08/22)
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- Design, synthesis, and urease inhibition studies of a series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones
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A series of 4-amino-5-aryl-3H-1,2,4-triazole-3-thiones was synthesized by reaction of aryl hydrazides with CS2 and hydrazine hydrate. The synthesized compounds were characterized by spectroanalytical techniques, and their urease inhibition activity was evaluated using jack bean urease. All but one of the synthesized compounds were active, and two of them were found to be more potent than the standard, with 50% inhibition concentration (IC 50) values of 17.5 ± 0.52 and 4.3 ± 0.169 μM, respectively (standard IC 50 = 21.0 ± 0.11 μM). Tentative statements regarding the role of different functional groups in binding to the enzyme active site are also presented.
- Khan, Mahmood-Ul-Hassan,Hameed, Shahid,Yasin, Khawaja A.,Akhtar, Tashfeen,Khan, Khalid M.
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p. 479 - 484
(2011/08/03)
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- Synthesis of novel triazole derivatives of methyl 3-oxocholanate using microwave irradiation
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An efficient rapid method for the synthesis of new triazole derivatives derived from methyl 3-oxocholanate under microwave irradiation has been developed. These new compounds were characterised by 1H NMR, IR, ESI-MS spectra and elemental analyses. Some of these triazoles were tested for antibacterial activity against Staphylococcus aureus, Candida albicans and Escherichia coli.
- Yang, Jie,Cheng, YuYu,Shi, ZhiChuan,Zhao, ZhiGang
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p. 680 - 683
(2011/04/26)
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- Novel lead structures for p38 MAP kinase via FieldScreen virtual screening
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p38 MAP kinase has received considerable interest in the pharmaceutical industry and remains a valid and interesting target for the treatment of inflammation. To discover novel p38 inhibitors, we applied the ligand-based virtual screening technique, FieldScreen, to 1.2 million commercially available compounds. Fifty-eight diverse compounds were selected for biological analysis, using molecular field similarity to known inhibitors, while explicitly removing any structure that shared a scaffold with previously reported p38 inhibitors. Of these, 11 (19%) showed ≥20% inhibition of p38 at 10 μM. We chose to prepare analogues of two distinct chemical series resulting in a potential lead compound with pIC50 of 6.4. Modeling of SAR using FieldAlign, a ligand alignment protocol, was used to rationalize the SAR of the series of thiadiazole based inhibitors.
- Cheeseright, Timothy J.,Holm, Melanie,Lehmann, Frank,Luik, Sabine,Gottert, Marcia,Melville, James L.,Laufer, Stefan
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experimental part
p. 4200 - 4209
(2010/01/16)
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- Synthesis and anthelmintic activity of 3,6-disubstituted-7H-s-triazolo(3,4-b) (1,3,4) thiadiazines
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A series of 3,6-disubstituted-7H-s-triazolo (3,4-b) (1,3,4)thiadiazines was synthesized by the condensation of the appropriate 3-substituted-4-amino-5-mercapto (1,2,4) triazoles with substituted phenacyl bromides in alcoholic medium. These compounds have been studied for their in vivo anthelmintic activity in albino mice. A number of compounds showed promising activity when given by the oral route.
- Nadkarni,Kamat,Khadse
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p. 569 - 573
(2007/10/03)
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