3D-QSAR and docking studies on piperidine-substituted diarylpyrimidine analogues as HIV-1 reverse transcriptase inhibitors

Liu, Xin; Chen, Xuwang; Zhang, Lingzi; Zhan, Peng; Liu, Xinyong

doi:10.1007/s00044-015-1381-1

Cited by 12 publications

(3 citation statements)

References 26 publications

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“…Since the five CoMSIA descriptor fields—namely steric (S), electrostatic (E), hydrophobic (H), hydrogen bond donor (D) and acceptor (A)—are not totally independent from each other, different combinations of the five fields were used to obtain the best model [34,40,41]. The results of the 31 possible field combinations were shown in Figure 1 and the Q cv 2 value was used to assess the statistical qualities of these 3D-QSAR models.…”

Section: Resultsmentioning

confidence: 99%

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Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking

et al. 2016

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DNA repair enzyme O 6 -methylguanine-DNA methyltransferase (MGMT), which plays an important role in inducing drug resistance against alkylating agents that modify the O 6 position of guanine in DNA, is an attractive target for anti-tumor chemotherapy. A series of MGMT inhibitors have been synthesized over the past decades to improve the chemotherapeutic effects of O 6 -alkylating agents. In the present study, we performed a three-dimensional quantitative structure activity relationship (3D-QSAR) study on 97 guanine derivatives as MGMT inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Three different alignment methods (ligand-based, DFT optimization-based and docking-based alignment) were employed to develop reliable 3D-QSAR models. Statistical parameters derived from the models using the above three alignment methods showed that the ligand-based CoMFA (Q cv 2 = 0.672 and R ncv 2 = 0.997) and CoMSIA (Q cv 2 = 0.703 and The results indicated that the obtained binding interactions were consistent with the 3D contour maps. Overall, the combined results of the 3D-QSAR and the docking obtained in this study provide an insight into the understanding of the interactions between guanine derivatives and MGMT protein, which will assist in designing novel MGMT inhibitors with desired activity.

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Section: Resultsmentioning

confidence: 99%

“…The quality of 3D-QSAR models is usually sensitive to a specific alignment method [41,50]. In this study, three different alignment methods were employed to construct the 3D-QSAR models.…”

Section: Methodsmentioning

confidence: 99%

Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking

et al. 2016

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“…The PLS statistical parameters of CoMFA and CoMSIA models are listed in ►Table 4, which are useful tools to derive multilinear relationships between independent and dependent variables, together with a cross-validation test were used for the generation and internal validation of the CoMFA and CoMSIA models. 35 As ►Table 4 shows, CoMFA and CoMSIA models were developed, and the final models were selected according to the statistical parameters.…”

Section: Comfa and Comsia Analysismentioning

confidence: 99%

3D-QSAR and Docking Studies on Pyrimidine Derivatives of Second-Generation ALK Inhibitors

Jiang

Song

Qiu

et al. 2022

Pharmaceutical Fronts

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Anaplastic lymphoma kinase (ALK) is a promising target for the treatment of non-small cell lung cancer. Under crizotinib treatment, drug resistance and progressive disease appeared after the point mutations arising in the kinase domain of ALK. Second-generation ALK inhibitors can solve the deficiencies of the first generation, especially the drug resistance in cancer chemotherapy. Ceritinib (LDK378), a pyrimidine derivative, for example, can inhibit the activity of ALK with an IC50 value of 40.7 nmol/L, and can experience disease progression after initial treatment with crizotinib. Unfortunately, clear structure–activity relationships have not been identified to date, impeding the rational design of future compounds possessing ALK inhibition activity. To explore interesting insights into the structures of pyrimidine derivatives that influence the activities of the second-generation ALK inhibitors, three-dimensional quantitative structure–activity relationship (3D-QSAR) and molecular docking were performed on a total of 45 derivatives of pyrimidine. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques were used to generate 3D-QSAR models. CoMFA and CoMSIA were performed using the Sybyl X 2.0 package. Molecular docking analysis was performed using the Surflex-Dock module in SYBYL-X 2.0 package. We found in the CoMFA model that the non-cross-validated r2 value was 0.998, the cross-validated q 2 value was 0.663, and the F statistic value was 2,401.970, while the r2 value was 0.988; q 2 value was 0.730, and F value was 542.933 in CoMSIA models, suggesting the good predictability of the CoMFA and CoMSIA models. 3D contour maps and docking results suggested that different groups on the core parts of the compounds could enhance the biological activities. Based on these results, the established 3D-QSAR models and the binding structures of ALK inhibitors obtained favor the prediction of the activity of new inhibitors and will be helpful in the reasonable design of ALK inhibitors in the future.

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QSAR, docking, and Molecular dynamic studies on the polyphenolic as inhibitors of β-amyloid aggregation

Mahmoodabadi

Ajloo

2016

Med Chem Res

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3D-QSAR and docking studies on piperidine-substituted diarylpyrimidine analogues as HIV-1 reverse transcriptase inhibitors

Cited by 12 publications

References 26 publications

Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking

Identification of the Structural Features of Guanine Derivatives as MGMT Inhibitors Using 3D-QSAR Modeling Combined with Molecular Docking

3D-QSAR and Docking Studies on Pyrimidine Derivatives of Second-Generation ALK Inhibitors

QSAR, docking, and Molecular dynamic studies on the polyphenolic as inhibitors of β-amyloid aggregation

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