86770-31-2Relevant articles and documents
Antimicrobial and antiproliferative study of chalcone clubbed 2,4-dimethylpyrrole-3-carboxamide derivatives: Synthesis and in vitro evaluation
Rasal, Nishant Kisan,Jagtap, Sangeeta Vijay,Bhange, Dattatraya Soma
, p. 119 - 130 (2021/10/06)
The presented study explores the anticancer potency of a novel series of chalcone clubbed 2,4-dimethyl-1H-pyrrole-3-carboxamide derivatives. In vitro antimicrobial screening concluded that five compounds are potential against Candida albicans having inhibition of growth in the range of 46.38%–73.05% against at the concentration of 32 μg/mL. The antiproliferative screening against 60 cancer cell lines revealed that seven compounds have great potential against the various types of cancer cell lines with inhibition of growth in the range of 41%–71%. The structure–activity relationship study concluded that the hydrazide bond is more significant than the carboxamide bond. In silico study of highly potential derivatives obeys each parameter of Lipinski rule of five and qualified drug-likeness behavior. The presented pyrrole-chalcone template delivered various candidates as anticancer agents, and those could be a potential scaffold to develop the new anticancer drug.
Synthesis, biological evaluation, and in silico study of pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid derivatives
Rasal, Nishant K.,Sonawane, Rahul B.,Jagtap, Sangeeta V.
, (2020/10/22)
A potential molecular hybridization strategy was used to develop 24 novel pyrazoline-conjugated 2,4-dimethyl-1H-pyrrole-3-carboxylic acid and amide derivatives. The preliminary in vitro antimicrobial assay delivered four potential derivatives with growth inhibition in the range of 50.87–56.60% at the concentration of 32 μg/ml. In the search of an anticancer candidate, all derivatives were screened by NCI-60 at 10 μM concentration, revealing that 12 derivatives were potential agents against the various types of cancer cell lines, with growth inhibition in the range of 50.21–108.37%. The in vitro cytotoxicity assay against the cell line HEK293 (human embryonic kidney cells) and the hemolysis assay of the representative potent compounds propose their potential for a good therapeutic index. In silico studies of the most potent derivatives qualified their significant pharmacokinetic properties with good predicted oral bioavailability and their adherence to Lipinski's rule of five for druglikeness. A molecular docking study against VEGFR-2 with the best-scored conformations reinforced their anticancer potency. The docking study of the most potent compound against VEGFR-2 with the best-scored conformations displayed a binding affinity (?9.5 kcal/mol) comparable with the drug sunitinib (?9.9 kcal/mol) and exhibited that tighter interactions at the active adenosine triphosphate site might be responsible for anticancer potency.
Development of a novel conjugatable sunitinib analogue validated through in vitro and in vivo preclinical settings
El Mubarak, Mohamed A.,Leontari, Iliana,Efstathia, Giannopoulou,Vrettos, Eirinaios I.,Shaikh, Abdul kadar,Konstantinos, Siatis E.,Danika, Charikleia,Kalofonos, Haralabos P.,Tzakos, Andreas G.,Sivolapenko, Gregory B.
, p. 515 - 523 (2018/07/06)
Sunitinib is an oral FDA/EMEA approved multi-targeted tyrosine kinase inhibitor. It possesses anti-angiogenic and antitumor activity against a variety of advanced solid tumors. However, its chemical core does not allow a potential linkage to tumor-homing elements that could eventually enhance its potency. Therefore, a novel linkable sunitinib derivative, designated SB1, was rationally designed and synthesized. The pharmaceutical profile of SB1 was explored both in vitro and in vivo. Mass spectrometry and NMR spectroscopy were utilized for characterization, while MTT assays and LC-MS/MS validated protocols were used to explore its antiproliferative effect and stability, respectively. Cytotoxicity evaluation in three glioma cells showed that SB1 preserved the antiproliferative effect of sunitinib. SB1 was stable in vitro after 24 h incubation in mouse plasma, while both agents exhibited bioequivalent pharmacokinetic characteristics after i.v. administration in Balb/c mice. To evaluate the levels of SB1 in mouse plasma, a novel analytical method was developed and validated in accordance to the US FDA and the EU EMA guidelines. We formulated a novel linkable sunitinib analog exhibiting similar antiproliferative and apoptotic properties with native sunitinib in glioma cell lines. Both SB1 and native sunitinib showed identical in vitro stability in mouse plasma and pharmacokinetics after i.v. administration in Balb/c mice.
