831-71-0Relevant articles and documents
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.
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.
Synthesis and biological activity of 5-nitrofuran-containing (1,3,4-thiadiazol-2-yl)piperazine moieties as a new type of anti-Helicobacter pylori heterocycles
Moshafi, Mohammad Hassan,Yahya-Meymandi, Azadeh,Sadat-Ebrahimi, Seyed Esmaeil,Emami, Saeed,Nakhjiri, Maryam,Siavoshi, Farideh,Omrani, Maryam,Vosooghi, Mohsen,Alipour, Eskandar,Shafiee, Abbas,Foroumadi, Alireza
scheme or table, p. 201 - 210 (2012/01/14)
In order to find new and potent drug candidates for the treatment of Helicobacter pylori infections, in this study attention was focused on the synthesis and anti-H. pylori activity of a series of 5-(5-nitrofuran-2-yl)-1,3, 4-thiadiazoles containing piperazinyl functionality at the C-2 position of the 1,3,4-thiadiazole ring. The synthesis of 1-[5-(5-nitrofuran-2-yl)-1,3,4- thiadiazol-2-yl]piperazine derivatives 3a-h and pyrrolidine derivative 3i was achieved with a versatile and efficient synthetic route via 2-chloro-5-(5- nitrofuran-2-yl)-1,3,4-thiadiazole. The inhibitory activity of the new derivatives 3a-i against twenty clinical H. pylori strains was evaluated by the disc diffusion method and compared with the commercially available standard drug metronidazole. Resulting biological data indicated that most compounds exhibited strong inhibitory activity even at doses lower than 2 μg/disc (average zone of inhibition >20 mm) while metronidazole had little or no growth inhibition at this dose. Compound 3c containing the N-benzoylpiperazin-1- yl moiety showed the most potent inhibitory activity.
