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Part-IIIAdvances Dihydropyridines and …be considered as pure antagonists. At least two other types of binding sites have beenidentified in the Pgp in addition to the ATP site, one for transport and other formodulation. It is, therefore, unknown whether one or more pharmacophores exist in thePgp. The problem is complicated by the possible existence of mutant forms of the Pgp indifferent tumors with modified responses to modulators.Furthermore, the expression and function of the Pgp can be modulated by indirectmechanisms, such as interactions with membrane lipids 67 or inhibition of protein kinaseC. The reversal of MDR is established using tumor cells lines that are made resistant bythe exposure to an anticancer agent or by transfection of the mdr1 or mrp1 genes. Theparameter most widely used to show the activity of MDR reversal agents is reversal factor(RF). This type of assay assumes that the reversal agent does not show inherentcytotoxicity at the concentrations tested.The function and structure of ABC transporters along with their role and also in acquiredimmunodeficiency syndrome (AIDS) related lymphoma has been reviewed recently. 68-72The MDR modulators according to their chemical structures includes the arylalkylaminesincluding verapamil and its analogs (verapamil 1, devapamil 2 etc.), tiapamil and itsanalogs (tiapamil 3 and DMDP 4) and miscellaneous arylalkylamines (SR33557) 5,aryloxypropanolamines (propafenone-related compound 6, quinolyloxypropanolaminederivatives (MS-073) 7, anthranylamides (XR9576) 8, salicylamides 9 and relatedderivatives, nitrogen heterocycles including pyrrole derivatives (A-30312 10, HWL-1211), staurosporine and analogs (NA-381 12, NA-382 13 and SF-2370 14), indolederivatives (yohimbine 15 and reserpine 16), quinoline and isoquinoline derivatives(chloroquine 17, mefloquine 18 and quinine 19), acridin-9-ones and related compounds(GF-120918 (GG-918)) 20, quinazolines (AV-200) 21, phenothiazines and relatedheterocycles 73 (flupentixol 22 and trifluoperazine 23, pteridines and related condensedheterocycles (BIBW22BS) 24, 1,3,5-triazines and related compounds (S-9788) 25,oxygen heterocycles includes pyran derivatives 26, flavonoids (kaempferol 27 andquercetin 28 and coumarin derivatives (novobiocin 29), glutathione-related compounds asMRP reverters (MK-571) 30, cyclic peptides (cyclosporin A 31, SDZ PSC 833 32),depsipeptides (SDZ 280-446) 33 and macrolactones and macrolactams (FK506 34 andVX-710 35, steroids and related derivatives (megestrol acetate 36, medroxyprogesteroneacetate 37), terpenes and miscellaneous lipophilic compounds (taxuspine 38 and taxinine399