Matrix Metalloproteinase Inhibitors: A Review on Pharmacophore Mapping and (Q)SARs Results

Exploring QSAR and pharmacophore mapping of structurally diverse selective matrix metalloproteinase-2 inhibitors

“…These chemometric methods may also justify the superiority of nitrogen containing five‐membered rings over aromatic and straight chain moieties, because the former moiety may bring the hydrogen bond acceptor features closer to each other and thus, reduces the overall bulkiness of these molecules. The results of the current work considerably comply with the previously reported QSAR works on MMP inhibitors . For example, the current study highlighted the importance of lipophilicity which was previously described as one of the most important factors for higher activity .…”

“…Among 26 MMPs, MMP‐2 is intrinsically involved in the processes of tumour invasion and metastasis. It is now considered to be a potential target in the inhibition of metastasis of cancer. Apart from the catalytic zinc atom, MMP‐2 has two hydrophobic domains which are designated as S 1 ′ and S 2 ′ pockets.…”

“…Therefore, search for novel MMP‐2 inhibitors is still in progress in medicinal chemistry research. Literature review showed some 2D QSAR‐based studies were performed on MMP‐2 inhibitors that mainly highlighted the importance of hydrophobicity, molecular refractivity, molecular connectivity indices, electrotopological state atom indices and polarisability for MMP‐2 inhibition. In the current approach, an attempt has been taken to understand the structural and physicochemical requirements of a set of MMP‐2 inhibitors by the help of regression 2D quantitative structure activity relationship (2D QSAR) (conventional 2D QSAR), classification 2D QSAR (recursive partitioning (RP) and Bayesian modelling), 3D‐pharmacophore mapping and 3D QSAR (comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA)) methods.…”

Expression of MMP-15 and MMP-24 in atherosclerotic and nonatherosclerotic coronary arteries

“…It has been suggested that the limited information available on the biological properties and pathological role of MMPs and their inhibitors may have led to unsatisfactory results endothelial cells, macrophages, neutrophils, and lymphocytes. 25,26 MMPs have an important role in the remodeling process, both physiologically and pathologically, including atherosclerotic plaque formation and rupture, development of arterial aneurysms, and critical limb ischemia. 10,27 It has been reported that atherosclerotic human arteries contain increased amounts in clinical trials.…”

Keloids: a new challenge for nutrition

“…Approximately 40% of serum zinc is linked to alpha‐macroglobulin protein, which is a collagenase inhibitor 102 . Paradoxically, collagenase is also zinc dependent 102,103 . Since greater collagenase activity and consumption are evident in keloids, individuals with keloids could have smaller amounts of zinc available in the body.…”