79-19-6Relevant academic research and scientific papers
Diaryl-substituted thiosemicarbazone: A potent scaffold for the development of New Delhi metallo-β-lactamase-1 inhibitors
Li, Jia-Qi,Sun, Le-Yun,Jiang, Zhihui,Chen, Cheng,Gao, Han,Chigan, Jia-Zhu,Ding, Huan-Huan,Yang, Ke-Wu
, (2020/12/30)
The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging public health threat. Inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. A potent scaffold, diaryl-substituted thiosemicarbazone, was constructed and assayed with metallo-β-lactamases (MβLs). The obtained twenty-six molecules specifically inhibited NDM-1 with IC50 0.038–34.7 μM range (except 1e, 2e, and 3d), and 1c is the most potent inhibitor (IC50 = 0.038 μM). The structure-activity relationship of synthetic thiosemicarbazones revealed that the diaryl-substitutes, specifically 2-pyridine and 2-hydroxylbenzene improved inhibitory activities of the inhibitors. The thiosemicarbazones exhibited synergistic antimycobacterial actions against E. coli-NDM-1, resulted a 2–512-fold reduction in MIC of meropenem, while 1c restored 16–256-, 16-, and 2-fold activity of the antibiotic on clinical isolates ECs, K. pneumonia and P. aeruginosa harboring NDM-1, respectively. Also, mice experiments showed that 1c had a synergistic antibacterial ability with meropenem, reduced the bacterial load clinical isolate EC08 in the spleen and liver. This work provided a highly promising scaffold for the development of NDM-1 inhibitors.
Design, synthesis, and biological evaluations of (E)-2-(1-[2-mercapto-4-methyl-1-phenyl-1H-imidazol-5-yl]ethylidene)hydrazinecarbothioamide derivatives as antimicrobial agents
Daraji, Drashti G.,Jayanthi, Sivaraman,Patel, Hitesh D.,Rajani, Dhanji P.
supporting information, (2021/12/08)
In recent year, the development of new drugs as antibacterial agents is an important resolution to overcome drug-resistant pathogens. Imidazole derivatives were synthesized using the microwave irradiation method and were characterized using spectral analysis techniques such as proton nuclear magnetic resonance, mass, and Fourier transform infrared spectroscopy. All the analogous were assessed for their in vitro antimicrobial activity and in silico; minimum inhibition concentration values of some conjugates were evaluated against extended spectrum beta-lactamases, vancomycin-resistant enterococci, and Methicillin-resistant Staphylococcus aureus strains from clinical samples. All the analogous were used as ligands in molecular docking and adsorption, distribution, metabolism, and excretion against saDHPS. Furthermore, compounds were also examined for their in vitro antituberculosis and antimalarial activity.
Electrochemical characterization of isatin-thiosemicarbazone derivatives
Bandeira, Katlen Christian Tribuzy,Bohs, Lucas Martins Correa,Bresolin, Leandro,Gervini, Vanessa Carratu,Godoi, Marcelo,Justim, Juliano da Rosa,Martins, Bianca Barreto,Melo, Ana Paula Lopes de,Peixoto, Carlos Roberto de Menezes
, (2021/11/26)
Abstract: Herein, we have notably described the electrochemical behavior of four isatin-thiosemicarbazone derivatives. In this regard, cyclic voltammograms of isatin-3-thiosemicarbazone (ITSC), isatin-3-(N4-benzylthiosemicarbazone) (ITSC-Ph), 1-(5-nitro-2-oxoindolin-3-ylidene)thiosemicarbazide (NO2-ITSC) and 1-(5-nitro-2-oxoindolin-3-ylidene)-4-phenylthiosemicarbazide (NO2-ITSC-Ph) have demonstrated an irreversible oxidation process. More specifically, the generation of isatin and thiourea moieties as the final oxidation products was proposed. The cyclic voltammograms also demonstrate irreversible reduction processes of ITSC and ITSC-Ph in three steps. The proposed final products are 3-aminoindolin-2-one and thiourea moieties. In the cyclic voltammograms of NO2-ITSC and NO2-ITSC-Ph, five reduction processes were observed: three of them due to reduction of the nitro group. It was proposed that the formation of 5-hydroxyamino-3-iminoindolin-2-one and the thiourea moieties would be the final products. Graphic abstract: [Figure not available: see fulltext.] Electrochemical characterization of four isatin thiosemicarbazone derivatives is described. The compounds are irreversibly oxidized and reduced. Isatin moieties and thiourea are proposed to be the products generated after oxidation. Considering the reduction processes, the nitro group present at the isatin moiety is also reduced and influences the reduction products generated.
Insight on a new indolinone derivative as an orally bioavailable lead compound against renal cell carcinoma
Fouad, Marwa A.,Zaki, Mayssoune Y.,Lotfy, Raghda A.,Mahmoud, Walaa R.
, (2021/06/15)
A series of novel 3-indolinone-thiazolidinones and oxazolidinones 4a-k was synthesized via molecular hybridization approach and sequentially evaluated to explore its cytotoxic activity. The cytotoxicity screening pointed toward the N-cyclohexyl thiazolidinone derivative 4f that revealed promising renal cytotoxicity against CAKI-1 and UO-31 renal cancer cell lines with IC50 values 4.74 and 3.99 μM, respectively, which were comparable to those of sunitinib along with good safety threshold against normal renal cells. Further emphasis on compound 4f renal cytotoxicity was achieved via different enzyme assays and CAKI-1 and UO-31 cell cycle analysis. The results were supported by in silico studies to explore its physicochemical, pharmacokinetic and drug-likeness properties. Finally, compound 4f was subjected to an in vivo pharmacokinetic study through two different routes of administration showing excellent oral bioavailability. This research represents compound 4f as a promising candidate against renal cell carcinoma.
Novel indol-3-yl-thiosemicarbazone derivatives: Obtaining, evaluation of in vitro leishmanicidal activity and ultrastructural studies
da Silva, Paula Roberta,de Oliveira, Jamerson Ferreira,da Silva, Anekécia Lauro,Queiroz, Camila Marques,Feitosa, Ana Paula Sampaio,Duarte, Denise Maria Figueiredo Araújo,da Silva, Aline Caroline,de Castro, Maria Carolina Accioly Brelaz,Pereira, Valéria Rêgo Alves,da Silva, Rosali Maria Ferreira,Alves, Luiz Carlos,dos Santos, Fábio André Brayner,de Lima, Maria do Carmo Alves
, (2019/12/12)
Parasitic diseases still represent serious public health problems, since the high and steady emergence of resistant strains is evident. Because parasitic infections are distributed predominantly in developing countries, less toxic, more efficient, safer and more accessible drugs have become desirable in the treatment of the infected population. This is the case of leishmaniasis, an infectious disease caused by a protozoan of the genus Leishmania sp., responsible for triggering pathological processes from the simplest to the most severe forms leading to high rates of morbidity and mortality throughout the world. In the search for new leishmanicidal drugs, the thiosemicarbazones and the indole fragments have been identified as promising structures for leishmanicidal activity. The present study proposes the synthesis and structural characterization of new indole-thiosemicarbazone derivatives (2a-j), in addition to performing in vitro evaluations through cytotoxicity assays using macrophages (J774) activity against forms of Leishmania infantum and Leishmania amazonensis promastigote as well as ultrastructural analyzes in promastigotes of L. infantum. Results show that the indole-thiosemicarbazone derivatives were obtained with yield values varying from 32.09 to 94.64%. In the evaluation of cytotoxicity, the indole-thiosemicarbazone compounds presented CC50 values between 53.23 and 357.97 μM. Concerning the evaluation against L. amazonensis promastigote forms, IC50 values ranged between 12.31 and > 481.52 μM, while the activity against L. infantum promastigotes obtained IC50 values between 4.36 and 23.35 μM. The compounds 2d and 2i tested against L. infantum were the most promising in the series, as they showed the lowest IC50 values: 5.60 and 4.36 respectively. The parasites treated with the compounds 2d and 2i showed several structural alterations, such as shrinkage of the cell body, shortening and loss of the flagellum, intense mitochondrial swelling and vacuolization of the cytoplasm leading the parasite to cellular unviability. Therefore, the indole-thiosemicarbazone compounds are promising because they yield considerable synthesis, have low cytotoxicity to mammalian cells and act as leishmanicidal agents.
A novel 8-nitro quinoline-thiosemicarbazone analogues induces G1/S & G2/M phase cell cycle arrest and apoptosis through ROS mediated mitochondrial pathway
Arasakumar, Thangaraj,Athimoolam, Shunmuganarayanan,Mohan, Palathurai Subramaniam,Saravanan, Arjunan,Shyamsivappan, Selvaraj,Suresh, Thangaraj,Vivek, Raju
, (2020/03/11)
A series of novel 8-nitro quinoline-based thiosemicarbazone analogues were synthesized and characterized by various spectroscopic and single crystal X-ray analyses. The potent antitumor effects of synthesized compounds towards the cancer cells were evaluated by MTT assay. Amongst, the compound 3a exhibited the highest inhibitory activity and the compounds 3f and 3b were also showed significant activity. The molecular mechanistic studies of cell death have demonstrated that the treated potent compound 3a induced G1/S & G2/M phase cell cycle arrest and induced apoptosis via mitochondrial dysfunction and increased the production of cytotoxic ROS levels. The RT-PCR gene expression analysis revealed that the cell death induced by activation of caspase-3 dependent intrinsic apoptotic signaling pathway. Further, the molecular binding affinity of compounds with estrogen receptor alpha was calculated by molecular docking studies. Thus, novel 8-nitro quinoline-thiosemicarbazone analogues provide a unique tool for breast cancer therapeutic tactics.
Synthesis of novel quinoline-thiosemicarbazide hybrids and evaluation of their biological activities, molecular docking, molecular dynamics, pharmacophore model studies, and ADME-Tox properties
Darji, Drashti G.,Patel, Dhaval B.,Patel, Hitesh D.,Patel, Krupa R.,Rajani, Dhanji P.,Rajani, Smita D.
, (2020/02/13)
In the present study, a novel series of N-((substituted)carbamothioyl)-2,4-dimethylquinoline-3-carboxamide (7a-7s) was synthesized by microwave-assisted method. Structure of these derivatives was examined by spectroscopic techniques such as 1H NMR, 13C NMR, FT-IR, and ESI-MS. Further, the novel synthesized compounds were evaluated for their in-vitro biological activities against antibacterial, antifungal, antimalarial, and antituberculosis activity as well as for in-silico study. The antimalarial results demonstrated that compounds 7c and 7q (0.02 μg/mL) have notable potency against Plasmodium falciparum compared with chloroquine (0.02 μg/mL); compounds 7l (0.10 μg/mL), 7e, 7s (0.19 μg/mL), 7b, 7p (0.15 μg/mL), 7a, 7f, and 7f (0.25 μg/mL) also exhibited good activity against P. falciparum compared with quinine (0.26 μg/mL) as standard drug. Docking was performed on PFDHFR-TS, given the effect of compounds against the P. falciparum strain was excellent in comparison with standard drug. Molecular docking suggested that compounds 7b, 7i and 7c, 7e, and 7l closely bind with the active site of protein 3JSU and 4DP3, respectively, and compared with biological activity. We have also carried out molecular dynamics simulation on the best dock compound 7e complex with PDB: 3JSU to check the stability of docked complex and their molecular interaction. The calculated ADME-Tox descriptors for the synthesized compounds validated good pharmacokinetics properties, suggesting that these compounds could be used as hit for the development of the new active agents.
One-pot green synthesis of some novel n-substituted 5-amino-1,3,4-thiadiazole derivatives
Abdul Rahman, Mohd B.,Habibi, Azizollah,Khosravi, Sahar,Shahcheragh, Seyyed M.
supporting information, p. 517 - 522 (2020/07/17)
In the current study, a green, one-pot, three-component reaction was performed to prepare novel N-substituted 5-amino-1,3,4-thiadiazole derivatives. The thiadiazoles were obtained from the reaction of a ketene S,S-acetal of Meldrum’s acid or barbituric acid (as key intermediates), hydrazine, and isothiocyanate. The key advantages of this manner include environmentally safe reactions, high yield, appropriate reaction time, simple reaction conditions, and use of a green reaction solvent. The structure of thiadiazoles was determined based on the spectroscopic data.
Design, synthesis and biological evaluation of novel semicarbazone-selenochroman-4-ones hybrids as potent antifungal agents
Xu, Hang,Su, Xin,Liu, Xiao-qian,Zhang, Kai-peng,Hou, Zhuang,Guo, Chun
supporting information, (2019/10/19)
A series of novel 2,3-dihydro-4H-1-benzoselenin-4-one (thio)semicarbazone derivatives were designed and synthesized by using molecular hybridization approach. All the target compounds were characterized by HRMS and NMR and evaluated in vitro antifungal activity against five pathogenic strains. In comparison with precursor selenochroman-4-ones, the hybrid molecules in this study showed significant improvement in antifungal activities. Notably, compound B8 showed significant antifungal activity against other strains excluding Aspergillus fumigatus (0.25 μg/mL on Candida albicans, 2 μg/mL on Cryptococcus neoformans, 8 μg/mL on Candida zeylanoides and 2 μg/mL on fluconazole-sensitive strains of Candida albicans). Moreover, compounds B8, B9 and C2 also displayed most potent activities against four fluconazole-resistance strains. Especially the MIC values of the hybrid molecule B8 against fluconazole-resistant strains were in the range of 0.5–2 μg/mL. Therefore, the molecular hybridization approach in this study provided new ideas for the development of antifungal drug.
Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition
Ha?dys,Goldeman,Jewgiński,Wolińska,Anger,Rossowska,Latajka
, p. 577 - 586 (2018/09/29)
The group of 19 thiosemicarbazones (TSCs) were synthesized and its inhibitory activity toward mushroom tyrosinase and ability to inhibition of melanogenesis in B16 cells were investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. The obtained results allowed to make the structure-activity relationship (SAR) analysis. Kinetic studies revealed that TSCs 1, 2, 11 and 18 have better inhibitory properties than kojic acid, a reference compound, with the best inhibitory constant (Ki) value of 0.38 μM for TSC 2. According to SAR analysis, the smaller and less branched molecules exhibit higher affinity to the enzyme. Melanin production in B16 cells was inhibited by all investigated compounds at micromolar level. Most of compounds studied in this work can be considered as potent inhibitors of tyrosinase and melanogenesis. They may have broad application in food preservatives and cosmetics. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties.
