ALK-5 Inhibition: A Molecular Interpretation of the Main Physicochemical Properties Related to Bioactive Ligands

Araujo, Sheila Cruz; Silva, Danielle C; Gertrudes, Jadson Castro; Honório, Káthia Maria

doi:10.5935/0103-5053.20150172

Cited by 6 publications

(9 citation statements)

References 4 publications

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“…Then, the physicochemical and molecular descriptors of the TPs 2 , 3 , 5 , 7 , 8 , 9 and 10 were calculated with PaDEL descriptor software [52] . At this step, 2187 descriptors were calculated, and then, we carried out the following variable selection strategies based on previously reported works: [41,53–55] (i) Fisher's weight was calculated in order to identify the descriptors with most importance to distinguish the clusters identified on HCA (FW>1); (ii) we calculated Pearson correlation coefficients to identify the highly correlated variables (R>0.80) to both experimental values; (iii) three variables were selected with high correlations with biological activities and least correlations among them. The three descriptors were autoscaled before the PCA studies.…”

Section: Methodsmentioning

confidence: 99%

Cytotoxic Activity of Triterpenoids from Cheiloclinium cognatum Branches against Chronic and Acute Leukemia Cell Lines

Pereira

Evangelista

Júnior

et al. 2020

Chemistry & Biodiversity

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Cheiloclinium cognatum (Miers) A.C.Sm. is an endemic species of Brazilian Cerrado that belongs to Celastraceae family. The phytochemical study of C. cognatum branches led to the identification of ten triterpenoids (TPs), 3β-acyloxyurs-12-ene (1), friedelin (2), β-friedelinol (3), glut-5-en-3β-ol (4), α-amyrin (5), βamyrin (6), β-sitosterol (7), canophyllol (8), 29-hydroxyfriedelan-3-one (9) and friedelane-3β,29-diol (10). TPs 4, 5 and 6 are described for the first Cheiloclinium genus and TPs 8 and 9 were isolated in expressive amounts. Their cytotoxic activities were evaluated against THP-1 and K562 leukemia cell lines. TPs 3 and 5 were the most active, exhibiting lower or similar IC 50 against both cell lines when compared to the controls. Their mechanisms of action were investigated suggesting an intrinsic mitochondrial pathway of apoptosis evidenced by up-regulation of BAK mRNA expression. Chemometric studies indicated that their activities may be related to their molecular size and shape as well as electronic interactions of C-3 hydroxy group with molecular targets.

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Section: Methodsmentioning

confidence: 99%

Cytotoxic Activity of Triterpenoids from Cheiloclinium cognatum Branches against Chronic and Acute Leukemia Cell Lines

Pereira

Evangelista

Júnior

et al. 2020

Chemistry & Biodiversity

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“…In this work, molecular modeling techniques were employed to aid in the design of new neolignan-based compounds with improved biological activity against T. cruzi . It is noteworthy to mention that, from molecular modeling studies and statistical models, valuable results have been obtained taking into account libraries of bioactive substances related to several biological targets [ 12 , 13 , 14 , 15 ]. In particular, computational techniques directed to studies related to CD can be considered as powerful tools to help in the discovery and the design of selective, potent, and safer drug candidates [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

et al. 2021

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In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD.

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“…Several studies attempt to inhibit the biological targets under study and one way to study the interaction processes between HER-2/EGFR and inhibitor molecules is employing molecular modeling methods, which are often employed in medicinal chemistry [6,13,14,15,16]. Using these techniques, it is possible to identify the interactions that occur between bioactive molecules and biological receptors.…”

Section: Introductionmentioning

confidence: 99%

Studies on the Dual Activity of EGFR and HER-2 Inhibitors Using Structure-Based Drug Design Techniques

Angelo

Almeida

Paula

et al. 2018

IJMS

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HER-2 and EGFR are biological targets related to the development of cancer and the discovery and/or development of a dual inhibitor could be a good strategy to design an effective drug candidate. In this study, analyses of the chemical properties of a group of substances having affinity for both HER-2 and EGFR were carried out with the aim of understanding the main factors involved in the interaction between these inhibitors and the biological targets. Comparative analysis of molecular interaction fields (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were applied on 63 compounds. From CoMFA analyses, we found for both HER-2 (r2 calibration = 0.98 and q2cv = 0.83) and EGFR (r2 calibration = 0.98 and q2cv = 0.73) good predictive models. Good models for CoMSIA technique have also been found for HER-2 (r2 calibration = 0.92 and q2cv = 0.74) and EGFR (r2 calibration = 0.97 and q2cv = 0.72). The constructed models could indicate some important characteristics for the inhibition of the biological targets. New compounds were proposed as candidates to inhibit both proteins. Therefore, this study may guide future projects for the development of new drug candidates for the treatment of breast cancer.

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ALK-5 Inhibition: A Molecular Interpretation of the Main Physicochemical Properties Related to Bioactive Ligands

Cited by 6 publications

References 4 publications

Cytotoxic Activity of Triterpenoids from Cheiloclinium cognatum Branches against Chronic and Acute Leukemia Cell Lines

Cytotoxic Activity of Triterpenoids from Cheiloclinium cognatum Branches against Chronic and Acute Leukemia Cell Lines

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

Studies on the Dual Activity of EGFR and HER-2 Inhibitors Using Structure-Based Drug Design Techniques

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