Current Medicinal Chemistry - Volume 8, Issue 3, 2001

The first paper reporting on a potentially important medical property of a non-antimicrobial tetracycline appeared in 1987. Since then, a literature of over 75 papers has supported the therapeutic potential of this class of compounds. In this review, this literature is grouped and organized with commentary on the data which has been published to date. The biomedical applicability of these discoveries obviously covers a wide ran Read More

CMTs are analogs of tetracyclines, which are chemically modified to eliminate their antimicrobial efficacy but which retain their inhibitory activity against matrix metall oproteinases. These compounds have been found to inhibit connective tissue breakdown in animal models of diseases such as periodontitis, arthritis and cancer. Because CMTs exhibit different in vivo efficacy in these various models of disease, the current study Read More

CMT-3 is a NON-ANTIMICROBIAL tetracycline (TC), chemically modified to enhance its collagenase-inhibitory property. This property is therapeutically useful in treating diseases such as periodontitis, cancer and arthritis. CMT-3 was labeled with tritium ( 3 H) at Carbon 7. Four adult male Sprague-Dawley rats (350-400 g body weight) were gavaged once with a mixture of cold CMT-3 and ( 3 H) CMT-3 (750 mu Ci). An a Read More

Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2 gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and Read More

COLO 205 is a cell line derived from a human colon carcinoma with high degradative activity towards extracellular matrix (ECM). It has been shown that COLO 205 cells produce matrix metalloproteinases (MMPs). MMPs are a family of enzymes known to degrade components of the ECM and have been implicated in tumor invasion. In the present study, we have analyzed the multiple effects of chemically modified tetracyclines Read More

Tetracyclines such as chlortetracycline and doxycycline with antimicrobial activity were reported to possess cytostatic and cytotoxic activity against mammalian tumor cells, often at high doses. Non-antimicrobial chemically modified tetracyclines (CMTs), with limited systemic toxicity but with significant tumor cell toxicity and anti-metastatic activity, are attractive for long term treatment for cancer. We recently reported one su Read More

Cutaneous wound healing is a complex process involving interactions of various cell types. Skin, in addition to certain other organs, is dependent on estrogen and estrogen-deficiency is associated with impaired wound healing. Wound healing involves the action of collagenolytic matrix metalloproteinases (MMPs). We investigated the expression and localization of collagenolytic MMPs -8 and -13 by collagenase activity as Read More

Recent studies have demonstrated that tetracyclines can reduce bone loss in the ovariectomized (OVX) rat model of osteoporosis. In the current study, a non-antimicrobial, chemically modified doxycycline (CMT-8), alone or in combination with a bisphosphonate (Clodronate), was evaluated in this model. Forty-two, 6month old, female rats were randomly assigned to the following groups, (6/ group): a) sham/vehicle, b) OVX/vehi Read More

Diabetes mellitus in rats is characterized by excessive activity of several matrix metalloproteinases (MMPs), notably collagenase(s) and gelatinase(s), in skin, gingiva, and other tissues. A number of tetracyclines (TCs), both antimicrobial compounds as well as chemically modified non-antimicrobial TC analogues (CMTs) are known to possess potent inhibitory activity against these enzymes. Three conventional antimicrob Read More

The etiology of inflammatory disorders involves many cellular, plasmatic and humoral pathways of signaling culminating in the production of enzymatic and free radical mediated tissue damage. Multiple redundant pathways of initiation and elusive temporal expression of initiators pose formidable barriers to effective treatment. Nowhere is this more evident than in the adult respiratory distress syndrome (ARDS), a syste Read More