Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase（IN） inhibitor approved by the United States Food and Drug Administration（US FDA）, were designed, synth...Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase（IN） inhibitor approved by the United States Food and Drug Administration（US FDA）, were designed, synthesized and characterized by ^1H NMR, IR and MS. The biological activities of these compounds against HIV-1 IN in vitro were evaluated. The assay results indicate that the replacement of pyrimidinone with furanone decreased the inhibitory activity of the compounds to HIV-1 IN. Compounds 3i, 3j and 3t show moderate inhibitory activity against HIV-1 IN and selectively inhibit the strand transfer reaction.展开更多
As one of the three viral encoded enzymes of HIV-1 infection, HIV-1 integrase has become an attractive drug target for the treatment. Diketoacid compounds （DKAs） are one kind of potent and selective inhibitors of HI...As one of the three viral encoded enzymes of HIV-1 infection, HIV-1 integrase has become an attractive drug target for the treatment. Diketoacid compounds （DKAs） are one kind of potent and selective inhibitors of HIV-1 IN. In the present work, two three-dimensional QSAR techniques （CoMFA and CoMSIA） were employed to correlate the molecular structure with the activity of inhibiting the strand transfer for 147 DKAs. The all-oritation search （AOS） and all-placement search （APS） were used to optimize the CoMFA model. The diketo and keto-enol tautomers of DKAs were also used to establish the CoMFA models. The results indicated that the enol was the dominant conformation in the HIV-1 IN and DKAs complexes. It can provide a new method and reference to identify the bioactive conformation of drugs by using QSAR analysis. The best CoMSIA model, with five fields combined, implied that the hydrophobic field is very important as well as the steric and electrostatic fields. All models indicated favorable internal validation. A comparative analysis with the three models demonstrated that the CoMFA model seems to be more predictive. The contour maps could afford steric, electrostatic, hydrophobic and H-bond information about the interaction of ligand-receptor complex visually. The models would give some useful guidelines for designing novel and potent HIV-1 integrase inhibitors.展开更多
In order to provide a facile and practical access to structurally diverse aryl -diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents. ...In order to provide a facile and practical access to structurally diverse aryl -diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents. The oxalylation of aryl methyl ketones, the key step to construct the pharmacophore of aryl -diketoacids, was con-siderably facilitated by a new combination of dimethyl oxalate as an oxalic source and sodium tert-butoxide as a base. A wide variety of aryl -diketoacids bearing different functional groups can be prepared rapidly in high yields at room temperature with this method, which has significant advantages over the previously reported procedures in a wider application range, much less amount of reagents, pretty higher yields and quite shorter reaction time. The bis-aryldiketoacids 3k and 3l, readily prepared by this method, displayed interesting and promising inhibitory ac-tivities against HIV-1 integrase and HIV-1 replication in cells.展开更多
The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase （IN）, which includes two important reactions, 3＇-processing and strand transfer, both catalyzed by HIV-1 IN. Disr...The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase （IN）, which includes two important reactions, 3＇-processing and strand transfer, both catalyzed by HIV-1 IN. Disrupting either of the reactions will fulfill the purpose of inhibiting the replication of HIV-1. In this paper, pharmacophore modeling and molecular docking are employed to investigate the inhibition mechanism of the HIV-1 IN strand transfer inhibitors （INSTIs）. Based on the results, we suggest that the inhibition mechanism of INSTIs involves the inhibitor chelating the cofactors Mg2＋ and its forming hydrogen bonds with some crucial residues adjacent to the DDE active center.展开更多
Integrase（IN） plays an essential role in the process of HIV-1 replication.IN inhibitors of diketo acid derivatives（DKAs） were analysed by the Comparative Molecular Field Analysis（CoMFA） and Comparative Molecular...Integrase（IN） plays an essential role in the process of HIV-1 replication.IN inhibitors of diketo acid derivatives（DKAs） were analysed by the Comparative Molecular Field Analysis（CoMFA） and Comparative Molecular Similarity Induces Analysis（CoMSIA） methods.A set of 42 compounds were randomly selected as the training set（35） and test set（7）.Firstly,a good pharmacophore（goodness of hit=0.787） was obtained and used to align ligands.Then,predictive models were constructed with the CoMFA and CoMSIA methods based on the pharmacophore alignment.As a result,the CoMS1A method yielded the best model with an r2 of 0.955 and a q2 of 0.665,which can predict the activities of the tested DKAs very well（r2=0.559）.Finally,DKAs were docked into IN,and the predicit modes were superimposed on the contour maps obtained from the best CoMSIA model.The superimposed maps gave a visualized and meaningful insight into the inhibitory behaviors,providing significantly useful information for the rational drug design of anti-IN agents.展开更多
Lipinski’s “Rule of Five” was introduced for predicting oral bioavailability to describe drug-like molecules. For the purpose of this research the rules were used to separate potential inhibitors of HIV-1 integrase...Lipinski’s “Rule of Five” was introduced for predicting oral bioavailability to describe drug-like molecules. For the purpose of this research the rules were used to separate potential inhibitors of HIV-1 integrase (1BIS.pdb) into two groups: drug-like and nondrug-like. If one of Lipinski’s “Rule of Five” was not followed the potential inhibitor was classified as nondrug-like. Thirty molecules were identified from the literature, twenty-four drug-like and six nondrug-like, that were docked into the active site of 1BIS.pdb (considered the non-mutated protein) and two mutant models, Y143R and N155H. These are two of the mutations that have led to increased resistance to HIV-1 integrase drugs such as raltegravir and elvitegravir. The computational software, ICM-Pro (Molsoft L.L.C.), was used to determine the estimated binding energy (EBE) of the drug/protein complex. It was found that the nondrug-like molecules generally had a more negative EBE, that is, tighter binding with 1BIS. pdb, though there were several exceptions in the drug-like group. With the protein mutant model Y143R, the majority of drug-like (58%) and nondrug-like molecules (67%) had tighter binding. However, for the mutant model N155H, there was the same percent (46%) of drug-like molecules with tighter binding with the mutant model as with 1BIS.pdb. The drug-like molecules were used when there was a ≥1 kcal/mole difference between 1BIS.pdb and either of the two mutant models to suggest a pharmacophore with structural characteristics for an HIV-1 integrase inhibitor.展开更多
Virion infectivity factor（Vif） is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G（h-APOBEC3G） is a cytidine deaminase only expre...Virion infectivity factor（Vif） is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G（h-APOBEC3G） is a cytidine deaminase only expressed in ＂nonpermissive＂ cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors＇ took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in ＂nonpermissive＂ cells with a dose-responsive manner, but not in ＂permissive＂ cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.展开更多
A series of novel aromatic-linked polyamine macrocyclic derivatives have been synthesized. Their structures were confirmed by MS and ^1H NMR. These compounds exhibited potent anti-HIV-1 activities.
The title compound （C50H.44010） was synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c with a = 16.713（4）, b --- 13.189（3）, c = 1...The title compound （C50H.44010） was synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c with a = 16.713（4）, b --- 13.189（3）, c = 19.434（5） A, β = 104.411（4）°, Mr = 804.85, Dc = 1.288 g/cm3, V = 4149.2（17） A3, Z = 4, F（000） = 1696, #（MoKa） = 0.089 mm-1T = 296（2） K, 7279 independent reflections with 3172 observed ones （I 〉 2δ（/））, R = 0.0520 and wR = 0.1203 with GOF = 0.928 （R = 0.1464 and wR = 0.1657 for all data）. The calixarene moiety maintains the symmetric cone conformation through intramolecular O-H…O hydrogen bonds. Preliminary bioassays indicated that the title compound has a potent inhibitory activity against the strand transfer process of HIV-1 integrase.展开更多
Aim To determine the effect of VIR576, a dimeric 20-mer peptide potently inhibits HIV-1 entry, on antigen-specific T cell and non-antigen-specific T cell activation. Methods In vitro T-cell proliferation assays were e...Aim To determine the effect of VIR576, a dimeric 20-mer peptide potently inhibits HIV-1 entry, on antigen-specific T cell and non-antigen-specific T cell activation. Methods In vitro T-cell proliferation assays were estalished to investigate the potential effect of FP16, VIR576 on the proliferation of A2b cells in response to MOG35-55. A fluorescence-based binding assay using Rhodamine （Rho）-conjugated VIR576 was estalished to e- valuate the potential interaction between VIR576 and TCR-TMD. Fluorescence confocal microscopy was used to to study whether VIR576 could colocalize with CD4 molecule in the CD4 ＋ T cell membrane to interact with TCR. Re- suits The effects of VIR576 on the proliferation of MOG-specific A2b T cells in response to the stimulation of MOG 35 -55 peptide wasevaluated. VIR576 itself could directly inhibit antigen-specific T-cell activation. Further studies confirmed that VIR576 also inhibited the proliferation of splenocytes and primary CD4 ＋ CD25- T cells iso- lated from the spleens of DOll. 10 OVA Tg mice in response to OVA stimulation in vitro. However, VIR576 had no effect on the proliferation of normal mouse splenocytes and T lymphocytes stimulated with Con A or anti-CD3 anti- body. The FRET assay confirmed that VIR576 effectively binds to the core peptide （CP） , corresponding to the N- terminal 9-residue region of TCR-TMD. Confocal microscopy revealed that VIR576 colocalizes with CD4 on the ac- tivated CD4 ＋ T-cell membrane, particularly within the activation cluster including re-assembled CD4 and TCR mol- ecules. Conclusion These results suggest that VIR576 is effective in suppressing antigen-specific T-cell activa- tion, but it has no effect on non-specific T-cell proliferation, and VIR576 has the ability to down-regulate antigen- specific T-cell activation by interaction with TCR transmembrane domain.展开更多
CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), not only plays a significant role in inflammatory responses, but also correlates with HIV-1 infection and cancer progression. Recently, ...CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), not only plays a significant role in inflammatory responses, but also correlates with HIV-1 infection and cancer progression. Recently, blocking of CCR5 has been considered as an effective strategy in HIV-1/cancers therapy. So far, only Maraviroc has been approved by FDA in 2007, while the other CCR5 inhibitors have failed in their clinical trials. In this study, a highly selective structure-based pharmacophore model was constructed, validated, and applied for virtual screening to retrieve novel CCR5 inhibitors from NCI database. Finally, one potential CCR5 inhibitor candidate, NSC13165, was identified after molecular docking, molecular dynamics (MD) simulations, binding free energy analyses and ADMET prediction. Docking and MD simulation results not only suggested that NSC13165 reserves the common binding mode of the most known CCR5 inhibitors, but also provided important insights toward the allosteric inhibition mechanism of CCR5. The results of binding free energy analyses indicated that the binding affinity of NSC13165 is much better than that of Maraviroc and that van der Waals interaction is the key driving force during the binding process. ADMET prediction suggested that NSC13165 exhibits very low risk of causing lethal side effects. Altogether, our results strongly suggest that NSC13165 has great potential to serve as a novel CCR5 inhibitor, which may be further tested in vitro/in vivo as a drug target for HIV-1/cancers therapy or be used as a lead compound for improving its efficacy through chemical modifications.展开更多
基金Supported by the National Natural Science Foundation of China(No.20872082)the Natural Science Foundation of Shandong Province,China(No.Y2007C060)
文摘Twenty novel furanone derivatives, based on the structure of raltegravir which was the first HIV-1 inte- grase（IN） inhibitor approved by the United States Food and Drug Administration（US FDA）, were designed, synthesized and characterized by ^1H NMR, IR and MS. The biological activities of these compounds against HIV-1 IN in vitro were evaluated. The assay results indicate that the replacement of pyrimidinone with furanone decreased the inhibitory activity of the compounds to HIV-1 IN. Compounds 3i, 3j and 3t show moderate inhibitory activity against HIV-1 IN and selectively inhibit the strand transfer reaction.
基金supported by the Natural Science Foundation of Zhejiang Province (Y. 4090578)
文摘As one of the three viral encoded enzymes of HIV-1 infection, HIV-1 integrase has become an attractive drug target for the treatment. Diketoacid compounds （DKAs） are one kind of potent and selective inhibitors of HIV-1 IN. In the present work, two three-dimensional QSAR techniques （CoMFA and CoMSIA） were employed to correlate the molecular structure with the activity of inhibiting the strand transfer for 147 DKAs. The all-oritation search （AOS） and all-placement search （APS） were used to optimize the CoMFA model. The diketo and keto-enol tautomers of DKAs were also used to establish the CoMFA models. The results indicated that the enol was the dominant conformation in the HIV-1 IN and DKAs complexes. It can provide a new method and reference to identify the bioactive conformation of drugs by using QSAR analysis. The best CoMSIA model, with five fields combined, implied that the hydrophobic field is very important as well as the steric and electrostatic fields. All models indicated favorable internal validation. A comparative analysis with the three models demonstrated that the CoMFA model seems to be more predictive. The contour maps could afford steric, electrostatic, hydrophobic and H-bond information about the interaction of ligand-receptor complex visually. The models would give some useful guidelines for designing novel and potent HIV-1 integrase inhibitors.
基金Shanghai Municipal Committee of Science and Technology (Nos.02QB14056 and 03DZ19219)the Chinese Academy of Sciences (KSCX1-SW-11)the Ministry of Personnel of China.
文摘In order to provide a facile and practical access to structurally diverse aryl -diketoacids, An improved and highly efficient oxalylation method was developed which employed commercially available and cheap reagents. The oxalylation of aryl methyl ketones, the key step to construct the pharmacophore of aryl -diketoacids, was con-siderably facilitated by a new combination of dimethyl oxalate as an oxalic source and sodium tert-butoxide as a base. A wide variety of aryl -diketoacids bearing different functional groups can be prepared rapidly in high yields at room temperature with this method, which has significant advantages over the previously reported procedures in a wider application range, much less amount of reagents, pretty higher yields and quite shorter reaction time. The bis-aryldiketoacids 3k and 3l, readily prepared by this method, displayed interesting and promising inhibitory ac-tivities against HIV-1 integrase and HIV-1 replication in cells.
基金supported by the National Natural Science Foundation of China (No. 30472166)the Tianjin Commission of Science and Technology (06YFGZSH07000)
文摘The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase （IN）, which includes two important reactions, 3＇-processing and strand transfer, both catalyzed by HIV-1 IN. Disrupting either of the reactions will fulfill the purpose of inhibiting the replication of HIV-1. In this paper, pharmacophore modeling and molecular docking are employed to investigate the inhibition mechanism of the HIV-1 IN strand transfer inhibitors （INSTIs）. Based on the results, we suggest that the inhibition mechanism of INSTIs involves the inhibitor chelating the cofactors Mg2＋ and its forming hydrogen bonds with some crucial residues adjacent to the DDE active center.
基金Supported by the National Natural Science Foundation of China（Nos.31100523,31171267,21173014） and the Beijing Outstanding Personnel Training Foundation,China（No.2012D005015000006）.
文摘Integrase（IN） plays an essential role in the process of HIV-1 replication.IN inhibitors of diketo acid derivatives（DKAs） were analysed by the Comparative Molecular Field Analysis（CoMFA） and Comparative Molecular Similarity Induces Analysis（CoMSIA） methods.A set of 42 compounds were randomly selected as the training set（35） and test set（7）.Firstly,a good pharmacophore（goodness of hit=0.787） was obtained and used to align ligands.Then,predictive models were constructed with the CoMFA and CoMSIA methods based on the pharmacophore alignment.As a result,the CoMS1A method yielded the best model with an r2 of 0.955 and a q2 of 0.665,which can predict the activities of the tested DKAs very well（r2=0.559）.Finally,DKAs were docked into IN,and the predicit modes were superimposed on the contour maps obtained from the best CoMSIA model.The superimposed maps gave a visualized and meaningful insight into the inhibitory behaviors,providing significantly useful information for the rational drug design of anti-IN agents.
文摘Lipinski’s “Rule of Five” was introduced for predicting oral bioavailability to describe drug-like molecules. For the purpose of this research the rules were used to separate potential inhibitors of HIV-1 integrase (1BIS.pdb) into two groups: drug-like and nondrug-like. If one of Lipinski’s “Rule of Five” was not followed the potential inhibitor was classified as nondrug-like. Thirty molecules were identified from the literature, twenty-four drug-like and six nondrug-like, that were docked into the active site of 1BIS.pdb (considered the non-mutated protein) and two mutant models, Y143R and N155H. These are two of the mutations that have led to increased resistance to HIV-1 integrase drugs such as raltegravir and elvitegravir. The computational software, ICM-Pro (Molsoft L.L.C.), was used to determine the estimated binding energy (EBE) of the drug/protein complex. It was found that the nondrug-like molecules generally had a more negative EBE, that is, tighter binding with 1BIS. pdb, though there were several exceptions in the drug-like group. With the protein mutant model Y143R, the majority of drug-like (58%) and nondrug-like molecules (67%) had tighter binding. However, for the mutant model N155H, there was the same percent (46%) of drug-like molecules with tighter binding with the mutant model as with 1BIS.pdb. The drug-like molecules were used when there was a ≥1 kcal/mole difference between 1BIS.pdb and either of the two mutant models to suggest a pharmacophore with structural characteristics for an HIV-1 integrase inhibitor.
基金the National Natural Science Foundation of China(No.30570363)Distinguished Young Scholars Fund of Jilin Province, China(No.20050112)the New Century Excellent Talents
文摘Virion infectivity factor（Vif） is one of the six accessory proteins of HIV-1 and is necessary for viral infectivity. Human Apolipoprotein B editing complex protein 3G（h-APOBEC3G） is a cytidine deaminase only expressed in ＂nonpermissive＂ cells and exhibits virus suppressive activity. With the aid of a Cullin-5 E3 ligase, Vif induces h-APOBEC3G degradation and with the destruction of this ligase, Vif is functionally inactive. Therefore, it is expected that blocking this E3 pathway would be a new therapeutic strategy against HIV-1 infection. In this article, the authors＇ took sequence alignment of the N-termini of Cullin-5 and three other members of the Cullin protein family, respectively. A set of small peptides has been synthesized based on the sequence comparison results and possible Vif-Cullin-5 interaction domains. Moreover, it has been demonstrated that several peptides can reduce virus infectivity in ＂nonpermissive＂ cells with a dose-responsive manner, but not in ＂permissive＂ cells. The results also indicate that the loss of viral infectivity may be because of the increase of APOBEC3G amount in the peptide-treated cells. It is concluded that peptides derived from Cullin-5 can block the APOBEC3G degradation induced by Vif and suppress HIV-1 infectivity. Therefore this study starts a novel strategy for the development of a new HIV-1 inhibitor.
基金supported by the National Basic Research Program of China(973 project:No.2004CB518908)the National Natural Science Foundation of China(No.30472093)to SLthe 0utstanding 0verseas Chinese Scholars Fund of Chinese Academy of Sciences(No.2005-2-6)to S.J.
文摘A series of novel aromatic-linked polyamine macrocyclic derivatives have been synthesized. Their structures were confirmed by MS and ^1H NMR. These compounds exhibited potent anti-HIV-1 activities.
基金supported by the National Natural Science Foundation of China(No.21102003)National Students'Innovation and Entrepreneurship Training Program(No.201210361094)Scientific Research Foundation for the Introduction of Talent and Young Teachers Scientific Research Foundation of Anhui University of Science&Technology(11214,2012QNY27)
文摘The title compound （C50H.44010） was synthesized and structurally determined by single-crystal X-ray diffraction method. It crystallizes in monoclinic, space group P21/c with a = 16.713（4）, b --- 13.189（3）, c = 19.434（5） A, β = 104.411（4）°, Mr = 804.85, Dc = 1.288 g/cm3, V = 4149.2（17） A3, Z = 4, F（000） = 1696, #（MoKa） = 0.089 mm-1T = 296（2） K, 7279 independent reflections with 3172 observed ones （I 〉 2δ（/））, R = 0.0520 and wR = 0.1203 with GOF = 0.928 （R = 0.1464 and wR = 0.1657 for all data）. The calixarene moiety maintains the symmetric cone conformation through intramolecular O-H…O hydrogen bonds. Preliminary bioassays indicated that the title compound has a potent inhibitory activity against the strand transfer process of HIV-1 integrase.
文摘Aim To determine the effect of VIR576, a dimeric 20-mer peptide potently inhibits HIV-1 entry, on antigen-specific T cell and non-antigen-specific T cell activation. Methods In vitro T-cell proliferation assays were estalished to investigate the potential effect of FP16, VIR576 on the proliferation of A2b cells in response to MOG35-55. A fluorescence-based binding assay using Rhodamine （Rho）-conjugated VIR576 was estalished to e- valuate the potential interaction between VIR576 and TCR-TMD. Fluorescence confocal microscopy was used to to study whether VIR576 could colocalize with CD4 molecule in the CD4 ＋ T cell membrane to interact with TCR. Re- suits The effects of VIR576 on the proliferation of MOG-specific A2b T cells in response to the stimulation of MOG 35 -55 peptide wasevaluated. VIR576 itself could directly inhibit antigen-specific T-cell activation. Further studies confirmed that VIR576 also inhibited the proliferation of splenocytes and primary CD4 ＋ CD25- T cells iso- lated from the spleens of DOll. 10 OVA Tg mice in response to OVA stimulation in vitro. However, VIR576 had no effect on the proliferation of normal mouse splenocytes and T lymphocytes stimulated with Con A or anti-CD3 anti- body. The FRET assay confirmed that VIR576 effectively binds to the core peptide （CP） , corresponding to the N- terminal 9-residue region of TCR-TMD. Confocal microscopy revealed that VIR576 colocalizes with CD4 on the ac- tivated CD4 ＋ T-cell membrane, particularly within the activation cluster including re-assembled CD4 and TCR mol- ecules. Conclusion These results suggest that VIR576 is effective in suppressing antigen-specific T-cell activa- tion, but it has no effect on non-specific T-cell proliferation, and VIR576 has the ability to down-regulate antigen- specific T-cell activation by interaction with TCR transmembrane domain.
文摘CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), not only plays a significant role in inflammatory responses, but also correlates with HIV-1 infection and cancer progression. Recently, blocking of CCR5 has been considered as an effective strategy in HIV-1/cancers therapy. So far, only Maraviroc has been approved by FDA in 2007, while the other CCR5 inhibitors have failed in their clinical trials. In this study, a highly selective structure-based pharmacophore model was constructed, validated, and applied for virtual screening to retrieve novel CCR5 inhibitors from NCI database. Finally, one potential CCR5 inhibitor candidate, NSC13165, was identified after molecular docking, molecular dynamics (MD) simulations, binding free energy analyses and ADMET prediction. Docking and MD simulation results not only suggested that NSC13165 reserves the common binding mode of the most known CCR5 inhibitors, but also provided important insights toward the allosteric inhibition mechanism of CCR5. The results of binding free energy analyses indicated that the binding affinity of NSC13165 is much better than that of Maraviroc and that van der Waals interaction is the key driving force during the binding process. ADMET prediction suggested that NSC13165 exhibits very low risk of causing lethal side effects. Altogether, our results strongly suggest that NSC13165 has great potential to serve as a novel CCR5 inhibitor, which may be further tested in vitro/in vivo as a drug target for HIV-1/cancers therapy or be used as a lead compound for improving its efficacy through chemical modifications.
