Multidrug resistance MDR

The unusual tolyporphin was isolated from the Pacific cyanophyte Tolypothrix nodosa and it has been shown that tolyporphin eliminates the multidrug resistance (MDR) in certain carcinoma sublines thus potentiating the cytotoxicity of anticancer drugs in these cell lines.2... 

ABC Transporters. Table 1 Substrates of ABC-transporters involved in multidrug resistance (MDR)... 

The multidrug resistance (MDR) phenomenon has first been described in cancer cells which were resistant against several structurally unrelated anticancer dtugs. Mechanistically a high expression of different ABC-transporters (P-gp, MRP) has been identified as the underlying factor. 

The multidrug resistance (mdr) reversing effect of the new phenothiazine complexes were tested on mouse T cell lymphoma cell lines. Trifluoperazine (TFP) was much more effective at the same concentration than verapamil. The efficacy of some metal coordination complexes [TFP-Cu(ll) and TFP-V(IV)] exceeded the action of TFP alone. Chlorpromazine (CPZ) or CPZ-Pt(ll) complex had the same or less effect than verapamil or promethazine (Pz) used as a control. 

One interesting example of the potential importance of intracellular pH gradients is found in the phenomenon of multidrug resistance (MDR). The MDR protein acts as a molecular pump, actively pumping chemotherapeutic agents out of the cell. Tumor cells, which are susceptible to chemotherapeutics have often a lower intracellular pH [178], which would lead to enhanced accumulation of these drugs in response to the pH differ-... 

Tanabe M, Ieiri I, Nagata N, Inoue K, Ito S, Kanamori Y et al. Expression of P-glycoprotein in human placenta relation to genetic polymorphism of the multidrug resistance (MDR)-l gene. J Pharmacol Exp Ther 2001 297(3) 1137-1143. 

Teodori E, Dei S, Martelli C, Scapecchi S, Gualtieri F (2006) The functions and structure of ABC transporters Implications for the design of new inhibitors of P-gp and MRP1 to control multidrug resistance (MDR). Curr Drug Targets 7 893-909. 

Multidrug resistance (MDR) is the name ascribed to the phenomenon whereby cancer cells and tumors develop resistance to chemotherapeutic agents. Conceptually, this can be viewed as a survival response whereby cancer cells endeavor to ward off cytotoxic compounds. Mechanistically, MDR is typically mediated by overexpression of P-glycoprotein (P-gp aka ABCB1) or other plasma membrane ATPases that export cytotoxic drugs used in chemotherapy, thereby reducing their efficacy. 

Flavonoids are known to inhibit the function of many ATP-binding proteins, such as mitochondrial ATPase, myosin, Na/K and Ca plasma membrane ATPases, protein kinases, topoisomerase II, and multidrug resistance (MDR) proteins. In general, inhibition takes place through binding of the flavonoids to the ATP-binding site. Only two cases relevant to the inhibition of carcinogenesis by flavonoids" " will be discussed in detail. 

Cancer cells typically overexpress ATP-dependent transmembrane transporters capable of expelling a wide variety of chemically unrelated drugs used in cancer therapy. This phenomenon is known as multidrug resistance (MDR). Inhibition of MDR proteins, such as the P-glycoprotein (Pgp), to prevent drug efflux during cancer therapy has thus potential clinical value. 

Condensation of l-[4,6-bis(allylamino)-l,33-triazin-2-yl]-4-piperidone (32) with amines 30 and 31 afforded the verapamil-like analogs 33 and 34 which were synthesized as potential drugs able to revert multidrug resistance (MDR). Both compounds show chemosensitizing activity but maintain some cardiovascular action <99JMC1687>. 

The most recognized and studied mechanisms of drug resistance are attributed to multidrug resistance (MDR), gene amplification, DNA repair. 

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