Antitumor Active Trans-Platinum Compounds
Astrid Sigel, Helmut Sigel in Metal Ions in Biological Systems, 2004
JM216 (6, cis,trans,cis-[PtCl2(acetate)2(NH3)(cyclohexylamine)]), lead compound of a series of mixed ammine/amine dicarboxylates, has been specifically designed to circumvent the poor gastrointestinal absorption of cisplatin or carboplatin [9] and it is currently in phase III clinical trials [23]. In a panel of human ovarian carcinoma xenografts, JM216 was demonstrated to possess oral antitumour activity broadly equivalent to that of intravenously administered cisplatin or carboplatin [24]. Moreover in a panel of cisplatin-sensitive and cisplatin-resistant human tumour cell lines, JM216 showed a cytotoxic potency similar to that of cisplatin, along with the ability to overcome cisplatin resistance associated with reduced drug transport [25, 26]. The toxicological profile is similar to that of carboplatin, myelosuppression representing the dose-limiting toxicity [27]. The DNA-binding properties of JM216 on either naked DNA or within tumor cells are similar to those of cisplatin, although there are some differences in the nature of the adducts [28].
Ovotoxic Environmental Chemicals: Indirect Endocrine Disruptors
Rajesh K. Naz in Endocrine Disruptors, 2004
Chemotherapy is one of the most toxic exposures to humans as regards germ cell destruction.[120] Cyclophosphamide has been studied more thoroughly than most due to its widespread use as a chemotherapeutic agent. CPA induces loss of primordial follicles and can cause sterility. Phosphoramide mustard has been determined to be the antineoplastic and ovotoxic form of this chemical.[42,121] Mice were dosed with chemicals capable of forming specific metabolites of cyclophosphamide (phosphoramide mustard, phosphoramide mustard cyclohexylamine salt or trans-4-phenylcyclophosphamide; or acrolein, didechlorocyclophosphamide and allyl alcohol). Only those chemicals that released phosphoramide mustard induced ovarian toxicity. The greater potency of phosphoramide mustard-producing chemicals compared to CPA in mice was attributed to a bypassing of detoxification steps, allowing more toxic metabolite to reach the ovary.[42] Metabolism of cyclophosphamide is thought to occur in the liver with uptake of the reactive metabolites from the blood to the ovary.[121] However, the possibility exists for detoxification of toxic metabolites in specific regions of the ovary, which might explain the follicle-stage-specific toxicity.
Nonnutritive Dietary Supplements in Pediatrics
Fima Lifshitz in Childhood Nutrition, 2020
Cyclamate—Cyclamate (cyclohexanesulfamate) (Figure 5) was discovered in 1937, approved for use as a sweetener in 1949, and was placed on the original GRAS list. It was banned by the FDA in 1970 because of evidence suggesting it was a carcinogen. In Canada and continental Europe, cyclamate has not been banned, and the acceptable daily intake is set at 11 mg/kg body weight. Cyclamate is usually found in foods as the calcium or sodium salt, often in a 10:1 mixture with saccharin. It is 30 × sweeter than glucose, is not heat labile, and has a long shelf life.37 It is slowly and only partially absorbed and is excreted largely unchanged in the urine.38 A metabolite, cyclohexylamine, has been identified in human urine following cyclamate administration.39 It is considered more toxic than cyclamate, and there is evidence that large doses can produce testicular atrophy in animals.38 The FDA ban in 1970 was precipitated by a long-term study where rats who were fed mixtures of cyclamate, saccharin, and cyclohexylamine showed an increased incidence of bladder tumors.41 There has been continuing debate over the potential carcinogenicity of cyclamate. The National Academy of Science/National Research Council reviewed the evidence in 1985,40 and concluded that cyclamate alone is not a carcinogen. However, it was also concluded that cyclamate appears to have cancer-promoting or co-carcinogenic activity. A petition is currently pending before the FDA to reinstate cyclamate as a nonnutritive sweetener.19
Discovery of new 1H-pyrazolo[3,4-d]pyrimidine derivatives as anticancer agents targeting EGFRWT and EGFRT790M
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Ahmed A. Gaber, Mohamed Sobhy, Abdallah Turky, Hanan Gaber Abdulwahab, Ahmed A. Al-Karmalawy, Mostafa. A. Elhendawy, Mohamed. M. Radwan, Eslam B. Elkaeed, Ibrahim M. Ibrahim, Heba S. A. Elzahabi, Ibrahim H. Eissa
The designed compounds were synthesised as outlined in Schemes 1–3. Ethoxymethylene malononitrile 141 was allowed to react with phenylhydrazine to produce 5-amino-1-phenyl-1H-pyrazole-4-carbonitrile 244. Compound 2 underwent partial hydrolysis using alcoholic NaOH to produce carboxamide derivative 345. Fusion of compound 3 with urea afforded 1-phenyl-1,7-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4,6(5H)-dion 4. Chlorination of compound 4 using phosphorus oxychloride and phosphorus pentachloride produced 4,6-dichloro-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine 546. Stirring of compound 5 with aniline at room temperature afforded 4-chloro-N,1-diphenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-amine 647. The obtained compound 6 was heated with commercially available different amines, namely ethylamine, propylamine, aniline, and cyclohexylamine in the presence of triethylamine afforded the target compounds 7a,b, 8, and 9, respectively. The IR spectra of 7a,b, and 9 demonstrated stretching bands at a range of 2950 − 2980 cm−1 corresponding to CH aliphatic groups. The 1H NMR spectra were characterised with abroad singlet at approximately 7–8 ppm due to the additional NH group.
Synthesis and characterisation of thiobarbituric acid enamine derivatives, and evaluation of their α-glucosidase inhibitory and anti-glycation activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
M. Ali, Assem Barakat, Ayman El-Faham, Hessa H. Al-Rasheed, Kholoud Dahlous, Abdullah Mohammed Al-Majid, Anamika Sharma, Sammer Yousuf, Mehar Sanam, Zaheer Ul-Haq, M. Iqbal Choudhary, Beatriz G. de la Torre, Fernando Albericio
Compound 3g was synthesised from 2a and cyclohexylamine following the general procedure, affording the product as a white powder in 84% yield; mp 105 °C; IR (KBr, cm−1): 3302, 2958, 2908, 2866, 1614, 1587, 1545, 1504, 1438, 1409; 1H-NMR (DMSO-d6, δ, ppm): 10.61 (brs, 1H, NH), 8.25 (d, 1H, J = 15.6 Hz, CH=), 4.52 (m, 4H, 2CH2), 3.40 (m, 1H, CH), 1.98 (m, 2H, CH2), 1.83 (m, 2H, CH2), 1.78 (m, 2H, CH2), 1.47 (m, 2H, 2CH2), 1.28 (m, 2H, 2CH3); 13C-NMR (DMSO-d6, δ, ppm): 179.0, 163.2, 161.3, 158.4, 92.6, 59.3, 42.9, 42.3, 33.5, 24.9, 24.3, 12.5, 12.4; LC/MS (ESI): 310.43 [M + 1]+; Anal. Calcd for C15H23N3O2S: C, 58.23; H, 7.49; N, 13.58; Found: C, 58.39; H, 7.53; N, 13.78.
Novel uses of ketamine in the emergency department
Published in Expert Opinion on Drug Safety, 2022
Brian N. Corwell, Sergey M. Motov, Natalie L. Davis, Hong K. Kim
Ketamine, a cyclohexylamine compound, is a dissociative anesthetic agent that has been used in human and veterinary medicine for approximately 50 years [1]. Phencyclidine (PCP) and ketamine were favored as anesthetic agents as they lacked respiratory and cardiovascular depression frequently associated with other anesthetic agents [2]. PCP was associated with intense and prolonged emergence delirium and psychodysleptic effects that made it unfavorable for human use [2,3], thus ketamine was introduced as a safer alternative [4]. Ketamine primarily antagonizes the N-methyl-D-aspartate (NMDA) receptors to exert its dissociative anesthetic effect, though it also has pharmacologic activity at numerous receptor systems including opioid, nicotinic, muscarinic receptors, and ion channels [4,5]. Ketamine’s unique pharmacologic properties extend beyond the well-characterized dissociative anesthetic effects. Today, ketamine is undergoing a renaissance due to renewed interests and potential applicability in the management of pain, depression, and acute agitation [1,6–8].
Related Knowledge Centers
- Amine
- Aniline
- Aromaticity
- Organic Compound
- Aliphatic Compound
- Sodium Hydroxide
- Cyclamate
- Amine Alkylation
- Cyclohexanol
- Sugar Substitute