5470-48-4Relevant academic research and scientific papers
Synthesis, in vitro thymidine phosphorylase activity and molecular docking study of thiadiazole bearing isatin analogs
Ullah, Hayat,Liaqat, Anjum,Khan, Qudrat Ullah,Taha, Muhammad,Khan, Fahad,Rahim, Fazal,Uddin, Imad,Rehman, Zia Ur
, p. 213 - 224 (2021/09/09)
A series of seventeen analogs (1─17) were synthesized and characterized through different spectroscopic techniques such as 1H, 13CNMR, HR-EI-MS and were evaluated for in vitro thymidine phosphorylase inhibition. All compounds showed excellent to good thymidine phosphorylase activity having IC50 value ranging between 4.10 ± 0.20 and 54.60 ± 1.40?μM when compared with standard drug 7-deazaxanthine (IC50 = 38.68 ± 1.12?μM). Among the series, compounds 1 (IC50 = 8.30 ± 0.30?μM), 6 (IC50 = 6.30 ± 0.10?μM), 11 (IC50 = 8.40 ± 0.30?μM) and 16 (IC50 = 4.10 ± 0.20?μM) were found more potent. Potent compounds were further subjected to molecular docking study to identify their interactions with the active site of amino acid. Structure activity relationship was done for all analogs mostly based on substitution pattern on phenyl and isatin rings. Graphic abstract: [Figure not available: see fulltext.]
Synthesis, antimicrobial and antioxidant evaluation with in silico studies of new thiazole Schiff base derivatives
Ahmed, Junaid Uddin,Al-Macktuf, Abdullah,Haque, Md. Aminul,Islam, Md. Din,Nishino, Hiroshi,Rahman, Mohammad Mostafizur,Shah, Md. Shahazada
, (2021/10/19)
A series of nineteen thiazole Schiff base derivatives 2a-2s were synthesized (Scheme 1) and elucidated by spectral analyses (IR, 1H NMR and HRMS). The evaluation of their antimicrobial activities against two gram-positive, two gram-negative, an
Assessment of Thiosemicarbazone-Containing Compounds as Potential Antileukemia Agents against P-gp Overexpressing Drug Resistant K562/A02 Cells
Gu, Xiaoke,Guan, Mingyu,Jiang, Chunyu,Song, Qinghua,Li, Xin,Sun, Nan,Chen, Jing,Qiu, Jingying
, (2021/01/15)
P-Glycoprotein (P-gp) overexpression is considered to be the leading cause of multidrug resistance (MDR) and failure of chemotherapy for leukemia. In this study, seventeen thiosemicarbazone-containing compounds were prepared and evaluated as potential ant
Discovery of new coumarin-based lead with potential anticancer, cdk4 inhibition and selective radiotheranostic effect: Synthesis, 2d & 3d qsar, molecular dynamics, in vitro cytotoxicity, radioiodination, and biodistribution studies
Sarhan, Mona O.,Abd El-Karim, Somaia S.,Anwar, Manal M.,Gouda, Raghda H.,Zaghary, Wafaa A.,Khedr, Mohammed A.
, (2021/05/13)
Novel 6-bromo-coumarin-ethylidene-hydrazonyl-thiazolyl and 6-bromo-coumarin-thiazolylbased derivatives were synthesized. A quantitative structure activity relationship (QSAR) model with high predictive power r2 = 0.92, and RMSE = 0.44 predicted five compounds; 2b, 3b, 5a, 9a and 9i to have potential anticancer activities. Compound 2b achieved the best ?G of –15.34 kcal/mol with an affinity of 40.05 pki. In a molecular dynamic study 2b showed an equilibrium at 0.8 ? after 3.5 ns, while flavopiridol did so at 0.5 ? after the same time (3.5 ns). 2b showed an IC50 of 0.0136 μM, 0.015 μM, and 0.054 μM against MCF-7, A-549, and CHO-K1 cell lines, respectively. The CDK4 enzyme assay revealed the significant CDK4 inhibitory activity of compound 2b with IC50 of 0.036 μM. The selectivity of the newly discovered lead compound 2b toward localization in tumor cells was confirmed by a radioiodination biological assay that was done via electrophilic substitution reaction utilizing the oxidative effect of chloramine-t.131 I-2b showed good in vitro stability up to 4 h. In solid tumor bearing mice, the values of tumor uptake reached a height of 5.97 ± 0.82%ID/g at 60 min p.i.131 I-2b can be considered as a selective radiotheranostic agent for solid tumors with promising anticancer activity.
Thiosemicarbazones exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1)
Ge, Ying,Kang, Peng-Wei,Li, Jia-Qi,Gao, Han,Zhai, Le,Sun, Le-Yun,Chen, Cheng,Yang, Ke-Wu
, p. 574 - 579 (2021/07/17)
The superbug infection caused by metallo-β-lactamases (MβLs) carrying drug-resistant bacteria, specifically, New Delhi metallo-β-lactamase (NDM-1) has become an emerging threat. In an effort to develop novel inhibitors of NDM-1, thirteen thiosemicarbazones (1a-1m) were synthesized and assayed. The obtained molecules specifically inhibited NDM-1, with an IC50 in the range of 0.88–20.2 μM, and 1a and 1f were found to be the potent inhibitors (IC50 = 1.79 and 0.88 μM) using cefazolin as substrate. ITC and kinetic assays indicated that 1a irreversibly and non-competitively inhibited NDM-1 in vitro. Importantly, MIC assays revealed that these molecules by themselves can sterilize NDM-producing clinical isolates EC01 and EC08, exhibited 78-312-fold stronger activities than the cefazolin. MIC assays suggest that 1a (16 μg ml?1) has synergistic antimicrobial effect with ampicillin, cefazolin and meropenem on E. coli producing NDM-1, resulting in MICs of 4-32-, 4-32-, and 4-8-fold decrease, respectively. These studies indicate that the thiosemicarbazide is a valuable scaffold for the development of inhibitors of NDM-1 and NDM-1 carrying drug-resistant bacteria.
Design, synthesis, biological evaluation, QSAR analysis and molecular modelling of new thiazol-benzimidazoles as EGFR inhibitors
Abd El-Karim, Somaia S.,Ahmed, Nesreen S.,Anwar, Manal M.,El-Hallouty, Salwa M.,Srour, Aladdin M.
supporting information, (2020/08/06)
Heterocyclic rings such as thiazole and benzimidazole are considered as privileged structures, since they constitute several FDA-approved drugs for cancer treatment. In this work, a new set of 2-(2-(substituted) hydrazinyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl) thiazoles 4a-q were designed as epidermal growth factor receptor (EGFR) inhibitors and synthesized using concise synthetic methods. The new target compounds have been evaluated in vitro for their suppression activity against EGFR TK. Compounds 4n, 4h, 4i, 4a and 4d exhibited significant potency in comparison with erlotinib which served as a reference drug (IC50, 71.67–152.59 nM; IC50 erlotinib, 152.59 nM). Furthermore, MTT assay revealed that compounds 4j, 4a, 4f, 4h, 4n produced the most promising cytotoxic potency against the human breast cancer cell line (MCF-7) (IC50; 5.96–11.91 μM; IC50 erlotinib; 4.15 μM). Compound 4a showed promising activity as EGFR TK inhibitor as well as anti-breast cancer agent. In addition, 4a induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells. Moreover, 4a upregulated the oncogenic parameters; caspase-3, p53, Bax/Bcl-2 as well as it inhibited the level of PARP-1 enzyme. QSAR study was carried out for the new derivatives and it revealed the goodness of the models. Furthermore, molecular docking studies represented the binding modes of the promising compounds in the active pocket of EGFR.
A group of diphosphine-thiosemicarbazone complexes of palladium: Efficient precursors for catalytic C–C and C–N coupling reactions
Thapa, Kiran,Paul, Piyali,Bhattacharya, Samaresh
, p. 232 - 239 (2018/11/06)
Reaction of 4-R-benzaldehyde thiosemicarbazone (denoted in general as HL-R; where H stands for the dissociable acidic proton and R (R = OCH3, CH3, H, Cl and NO2) for the substituent) with [Pd(dppe)(EtOH)2]2+, generated in situ via interaction of [Pd(dppe)Cl2] (dppe = 1,2-bis(diphenylphosphino)ethane) with AgNO3 in hot ethanol, in the presence of triethylamine affords a group of orange complexes of the type [Pd(dppe)(L-R)]NO3. Structures of [Pd(dppe)Cl2] and [Pd(dppe)(L-OCH3)]NO3 have been determined by X-ray crystallography. In the [Pd(dppe)(L-R)]NO3 complexes, the thiosemicarbazone ligands are coordinated to the metal center as monoanionic bidentate N,S-donors forming five-membered chelate rings. The [Pd(dppe)(L-R)]NO3 complexes show intense absorptions in the visible and ultraviolet regions, which have been analyzed by TDDFT calculations. All the [Pd(dppe)(L-R)]NO3 complexes are found to efficiently catalyze Suzuki-type C–C and Buchwald-type C–N coupling reactions.
Synthesis and comparison of antileishmanial and cytotoxic activities of S-(?)-limonene benzaldehyde thiosemicarbazones with their R-(+)-analogues
Almeida Batista, Sabrina A.,Vandresen, Fábio,Falzirolli, Hugo,Britta, Elizandra,de Oliveira, Diogo N.,Catharino, Rodrigo R.,Gon?alves, Mateus A.,Ramalho, Teodorico C.,La Porta, Felipe A.,Nakamura, Celso V.,da Silva, Cleuza C.
, p. 252 - 262 (2018/11/24)
In this study, we explore a series of novel potential antiprotozoal S-(?)-limonene-based benzaldehyde thiosemicarbazones were synthesised and their activity effective against the extracellular promastigote form of Leishmania amazonensis examined. Likewise, in parallel, a series of R-(+)-limonene-based thiosemicarbazones previously synthesised by our research group and thiosemicarbazones lacking the monoterpenic moiety, were also biologically evaluated. Here, we report the combination of theoretical and experimental approaches, as well as statistical analysis, to investigate the effect of the monoterpenic group and its stereochemistry in the biological activity of benzaldehyde thiosemicarbazone derivatives, for the identification of their structure-activity relationship. The terpenic thiosemicarbazones displayed the highest activities, confirming that the monoterpenic moiety is essential for activity. Notably, among the compounds tested, the S-(?)-enantiomer of the 4-nitro-derivative (8d) presented considerably lower cytotoxicity than its R-(+)-analogue, emphasizing the importance of the stereochemistry. The most active derivative (8d) exhibited a potent antiprotozoal activity (IC50 2.4 μM) and high selectivity (SI > 1147). Also, theoretical calculations were carried out at the density functional theory (DFT) level to show that the Gibbs free energy and LUMO orbitals present an excellent correlation with the experimental IC50 values. Finally, the combination of all these results may in principle be extremely advantageous to a deeper chemical understanding, as well as, allows a rational alternative for the future development of new drugs that act against leishmaniasis.
Benzaldehyde thiosemicarbazone derivatives against replicating and nonreplicating Mycobacterium tuberculosis
Volynets, Galyna P.,Tukalo, Michail A.,Bdzhola, Volodymyr G.,Derkach, Nataliia M.,Gumeniuk, Mykola I.,Tarnavskiy, Sergiy S.,Starosyla, Sergiy A.,Yarmoluk, Sergiy M.
, p. 218 - 224 (2019/01/29)
In this article, we report a series of benzaldehyde thiosemicarbazone derivatives possessing high activity toward actively replicating Mycobacterium tuberculosis strain with minimum inhibitory concentration (MIC) values in the range from 0.14 to 2.2 μM. Among them, two compounds—2-(4-phenethoxybenzylidene)hydrazine-1-carbothioamide (13) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothioamide (20) also demonstrate submicromolar antimycobacterial activity against M. tuberculosis under hypoxia with MIC values of 0.68 and 0.74 μM, respectively. The activity of compounds 13 and 20 toward five investigated isoniazid-, rifampicin-, and fluoroquinolone-resistant M. tuberculosis isolates is similar to commercially available antituberculosis drugs. The compounds 13 and 20 possess good ADME properties and have low cytotoxicity toward human liver cells (HepG2). Therefore, 2-(4-phenethoxybenzylidene)hydrazine-1-carbothioamide (13) and 2-(3-isopropoxybenzylidene)hydrazine-1-carbothioamide (20) are valuable candidates for further preclinical studies.
Synthesis, anti-HIV activity, molecular modeling study and QSAR of new designed 2-(2-arylidenehydrazinyl)-4-arylthiazoles
Rauf, Amna,Kashif, Muhammad K.,Saeed, Bahjat A.,Al-Masoudi, Najim A.,Hameed, Shahid
, (2019/08/07)
Taking into consideration the eminence of 1,3-thiazoles in medicinal chemistry and in a view of procuring more pronounced biological contour, the synthesis of 2-(2-arylidenehydrazinyl)-4-arylthiazoles 6–43 was made possible by the cyclization reaction of thiosemicarbazones and α-bromoacetophenones. The thiosemicarbazones 5a-m were in turn synthesized from substituted benzaldehydes or acetophenones and thiosemicarbazide. Optimization of the reaction conditions was carried out in order to attain the target molecules in good yields. All the new compounds were evaluated in vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT4 cells using a MTT assay. Screening results indicated that compounds 32–34 are the only compounds in the series inhibiting HIV-1 and HIV-2 replication in cell cultures with IC50 of >2.71, >2.19 and > 1.71 μM, respectively. The molecular docking of compounds 32 and 34 with some amino acids of human immunodeficiency virus reverse transcriptase (HIV RT) were also studied. The preliminary quantum structure-activity relationship (QSAR) among the newly synthesized congeners was obtained by two methods, Multiple Linear Regression (MRL) and Genetic Function Approximation (GFA).
