Disease relevance of NSC30445

• A platinum(II) and 3 platinum(IV) ammine/cycloalkylamine homologous series were evaluated for cytotoxicity and biochemical pharmacology in murine leukemia L1210/0, cis-diamminedichloroplatinum(II)- resistant L1210/DDP, and diaminocyclohexaneplatinum-resistant L1210/1,2-diaminocyclohexane (DACH) cells [1].
• Platinum complexes derived from three isomers of 1,2-diaminocyclohexane have been synthesized and their antitumor activities were evaluated against ascites Sarcoma-180 [2].
• Phase-II trial of 1,2-diaminocyclohexane (4-carboxyphthalato) platinum (II) (DACCP) in non-small cell lung cancer [3].
• Differential antitumor activity and toxicity of isomeric 1,2-diaminocyclohexane platinum (II) complexes [4].

High impact information on NSC30445

• Intracellular biotransformation of platinum compounds with the 1,2-diaminocyclohexane carrier ligand in the L1210 cell line [5].
• Moreover, approximately 1 mol of H2O2 was released per mol of PQQ or lysyl oxidase upon aerobic incubation with cis-1,2-diaminocyclohexane, while approximately 2 mol of 3H+ were released from cis-[1,2-3H] 1,2-diaminocyclohexane per mol of PQQ or lysyl oxidase under corresponding conditions [6].
• All these interactions are shown to apply also when diA = dach (1,2-diaminocyclohexane), even though this chiral primary diamine has only small N-H atoms on each side of the coordination plane [7].
• Direct chiral resolution of tartaric acid by ion-pair capillary electrophoresis using an aqueous background electrolyte with (1R,2R)-(-)-1,2-diaminocyclohexane as a chiral counterion [8].
• Two interesting representatives of a new generation of platinum-based cytostatic drugs that are currently being tested in clinical trials are lobaplatin [1,2-diaminomethylcyclobutane platinum(II) lactate] and oxaliplatin [1,2-diaminocyclohexane platinum (II) oxalate] [9].

Biological context of NSC30445

• Protein binding is selective for DNA modified with cisplatin, [Pt(en)Cl2] (en, ethylenediamine), and [Pt(dach)Cl2] (dach, 1,2-diaminocyclohexane) but not with chemotherapeutically inactive trans-diamminedichloroplatinum(II) or monofunctionally coordinating [Pt(dien)Cl]Cl (dien, diethylenetriamine) complexes [10].
• Acquired drug resistance is a major drawback of using cisplatin in the treatment of cancer; however, analogs containing the 1,2-diaminocyclohexane (DACH) ligand can overcome this resistance [11].
• Preliminary phase I clinical study and pharmacokinetics of (1,2-diaminocyclohexane) (isocitrato) platinum (II) or PHIC [12].

Anatomical context of NSC30445

• Cell spreading, reorganization of actin filaments and release of oxygen metabolites (measured as luminol-amplified chemiluminescence) were used as criteria for cell activation on positively charged, hydrophilic 1,2-diaminocyclohexane, and negatively charged, hydrophobic hexamethylene-disiloxane [13].
• The chirality selectivity in the uptake of platinum (II) complexes with 1,2-cyclohexanediamine isomers as carrier ligand by human erythrocytes [14].

Associations of NSC30445 with other chemical compounds

• The cis but not the trans isomer of 1,2-diaminocyclohexane was also a potent irreversible inhibitor of lysyl oxidase, consistent with the interaction of both amino groups of vicinal diamines with an enzyme moiety [6].
• The 2,2/c,c complexes are particularly active in tissue culture in cells resistant both to cisplatin and its 1,2-diaminocyclohexane (dach) analogue [15].
• The cytotoxic activity was tested in vitro against L1210 cells sensitive to cis-diamminedichloroplatinum(II) (L1210/0), L1210 cells resistant to cis-diamminedichloroplatinum(II) (L1210/DDP), and L1210 cells resistant to 1,2-diaminocyclohexane platinum (L1210/DACH) [16].
• Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2-)-O,O'] platinum; Eloxatin) is a third-generation platinum compound with a 1,2-diaminocyclohexane (DACH) carrier ligand, which has a wide spectrum of anticancer activity in vitro systems and has displayed preclinical and clinical activity in a wide variety of tumors [17].
• Their formulas are [(cis-Pt(NH3)2)2(mu-OH)(mu-1,2,3-ta)][NO3]2 (2) (1,2,3-ta = 1,2,3-triazolate), [(Pt(R,R-dach))(mu-OH)(mu-pz)(Pt(S,S- dach))][NO3]2 (3) (dach = 1,2-diaminocyclohexane, pz = pyrazolate), and [(Pt(R,R-dach))(mu-1,2,3- ta)2(Pt(S,S-dach))][NO3]2 (4) [18].

Gene context of NSC30445

• The formation of the prognosed complexes [Pt(DACH)(L-Met-S,N)]+ and [Pt(DACH)(5'-GMP)2]2- (DACH = 1,2-diaminocyclohexane) could be proved directly by using CE-ESI-MS [19].

Analytical, diagnostic and therapeutic context of NSC30445

• We have previously reported the development of a two-column high performance liquid chromatography system for separation of platinum(II) complexes with the 1,2-diaminocyclohexane (DACH) carrier ligand (Mauldin et al., Anal. Biochem., 157: 129, 1986) [5].
• Platinum drugs with the 1,2-diaminocyclohexane (dach) carrier ligand have shown great promise in cancer chemotherapy, but little is known about their metabolism in the body [20].
• The direct separation of beta-aminoester enantiomers by HPLC on synthetic chiral stationary phases based on a pi-acidic derivative of trans 1,2-diaminocyclohexane as selector is described [21].

References