Mikä on MMP-2?
MMP-2
72 kDa Gelatinase, Gelatinase AKohdemolekyylit
- Gelatins, collagens I,IV, V, VII, X, XI, fibronectin, laminin, aggrecan, elastin, large tenascin C, vitronectin, β-amyloid protein precursor (157–159)
LÄHDE: SAR QSAR Environ Res. 2017 Dec 19:1-26. doi: 10.1080/1062936X.2017.1406986. [Epub ahead of print]
Multiple molecular modelling studies on some derivatives and analogues of glutamic acid as matrix metalloproteinase-2 inhibitors.
Abstract
Matrix metalloproteinase-2
(MMP-2) is a potential target in anticancer drug discovery due to its
association with angiogenesis, metastasis and tumour progression. In
this study, 67 glutamic acid derivatives, synthesized and evaluated as
MMP-2 inhibitors,
were taken into account for multi-QSAR modelling study
(regression-based 2D-QSAR, classification-based LDA-QSAR, Bayesian
classification QSAR, HQSAR, 3D-QSAR CoMFA and CoMSIA as well as
Open3DQSAR). All these QSAR studies were statistically validated
individually. Regarding the 3D-QSAR analysis, the Open3DQSAR results
were better than CoMFA and CoMSIA, although all these 3D-QSAR models
supported each other. The importance of biphenylsulphonyl moiety over
phenylacetyl/naphthylacetyl moieties was established due to its
association with favourable steric and hydrophobic characters. HQSAR,
LDA-QSAR and Bayesian classification QSAR studies also suggested that
the biphenylsulphonamido group was better than the
phenylacetylcarboxamido function.
Additionally, glutamines were proven to be far better inhibitors than isoglutamines.
Observations obtained from the current study were revalidated and supported by the earlier reported molecular modelling studies. Depending on these observations, newer glutamic acid-based compounds may be designed further in future for potent MMP-2 inhibitory activity.
Additionally, glutamines were proven to be far better inhibitors than isoglutamines.
Observations obtained from the current study were revalidated and supported by the earlier reported molecular modelling studies. Depending on these observations, newer glutamic acid-based compounds may be designed further in future for potent MMP-2 inhibitory activity.
KEYWORDS:
2D-QSAR; Bayesian classification QSAR, HQSAR, 3D-QSAR CoMFA, 3D-QSAR CoMSIA, Open3DQSAR; LDA-QSAR; MMP-2 inhibitorMiksi pitäisi kehittää erityinen MMP-2 inhibiittori?
Matrixmetalloproteinaasi-2 (gelatinaasi A) on potentiaalinen kohdemolekyyli antisyöpälääkkeiten etsinnässä, koska se liittyy angiogeneesiin, metastasoitumiseen ja tuumorin progredioitumiseen.
Matrix metalloproteinase-2 (MMP-2) is a potential target in anticancer drug discovery due to its association with angiogenesis, metastasis and tumour progression.
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