Mini Reviews in Medicinal Chemistry - Volume 20, Issue 9, 2020

Among the methods used for the treatment of cancer, chemotherapy is widely used, and it is by far one of the most unpleasant procedures given to a patient because of its severe side effects; while being necessary. One of the major problems in cancer chemotherapy is the limited selectivity of most of the drugs in current clinical use. Following administration, the active agent is distributed over the entire body and reaches not only the target cells or tissues but also interacts with healthy cells. In an attempt to overcome the side effects of anticancer drugs, the modification of the anticancer bioactive compounds has been a topic of active research for years. Numerous delivery systems such as drugcontaining liposomes, microencapsulation, nanoparticles, and water-soluble polymers have been used for the delivery of bioactive compounds to the site of action. Water-soluble polymeric conjugates and co-conjugates have remained the most outstanding delivery technique. This review will discuss the development of polymeric conjugates and co-conjugates of ferrocene in cancer research.

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.

Parkinson's Disease (PD) is the second most common neurodegenerative disease in the elderly population, with a higher prevalence in men, independent of race and social class; it affects approximately 1.5 to 2.0% of the elderly population over 60 years and 4% for those over 80 years of age. PD is caused by the necrosis of dopaminergic neurons in the substantia nigra, which is the brain region responsible for the synthesis of the neurotransmitter dopamine (DA), resulting in its decrease in the synaptic cleft. The monoamine oxidase B (MAO-B) degrades dopamine, promoting the glutamate accumulation and oxidative stress with the release of free radicals, causing excitotoxicity. The PD symptoms are progressive physical limitations such as rigidity, bradykinesia, tremor, postural instability and disability in functional performance. Considering that there are no laboratory tests, biomarkers or imaging studies to confirm the disease, the diagnosis of PD is made by analyzing the motor features. There is no cure for PD, and the pharmacological treatment consists of a dopaminergic supplement with levodopa, COMT inhibitors, anticholinergics agents, dopaminergic agonists, and inhibitors of MAO-B, which basically aims to control the symptoms, enabling better functional mobility and increasing life expectancy of the treated PD patients. Due to the importance and increasing prevalence of PD in the world, this study reviews information on the pathophysiology, symptomatology as well as the most current and relevant treatments of PD patients.

This review refers to the all-inclusive details of Lorcaserin Hydrochloride on comprehensive information about the synthesis, analytical methods, pharmacodynamics, pharmacokinetics, drug interactions and adverse effects. Lorcaserin Hydrochloride is chemically (R)-8-Chloro-1-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine hydrochloride. Lorcaserin HCl is a novel, synthetic, centrally-acting selective serotonin C (5-HT2c) receptor, l agonist, which results in increased satiety and decreased food consumption in patients. Headache, dizziness and nausea are the most common side effects associated with this drug. Lorcaserin HCl has two major metabolites, one conjugated with glucuronide called N-carbamoyl glucuronide which is excreted in urine and the second Lorcaserin N-sulfamate, which is circulated in the blood. Lorcaserin HCl is synthesized using four different schemes of which a six-step method that resulted in 92.3% yield with 99.8% of purity is employed for scale-up production. It is analyzed quantitatively in the plasma and brain tissue matrix of rats by Ultra Performance Liquid chromatographic (UPLC) method using MS-MS (Mass Spectrometric) detection.

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

Objective: The reaction of bis(4-amino-4H-1,2,4-triazole-3-thiol) with hydrazonoyl halides and α-halo-ketones gave a new series of bis-1,2,4-triazolo[3,4-b]thiadiazine derivatives. Methods: The structure of the new products was established on the basis of their elemental and spectral data (mass, 1H NMR, 13C NMR and IR) and an alternate method. Results: Several of the synthesized products were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HepG-2) and the results showed that compounds 16, 14 and 12 have promising activities (IC50 value of 24.8±9.1, 28.3±0.5, and 31±2.9μM, respectively) compared with Harmine reference drug (IC50 value of 22.4±1.11 μM). Conclusion: Moreover, molecular docking studies were performed to analyze the binding modes of the discovered hits into the active site of DYRK1A using iGEMDOCK.

Objective: Novel bis(1,4-dihydropyridine-3,5-dicarbonitrile) derivatives linked to aliphatic or aromatic cores via amide or ester-amide linkages were prepared and their structures were confirmed by several spectral tools. Methods: The synthesis of novel N,N'-(alkanediyl)bis(2-(2-(3,5-dicyano-2,6-dimethyl-1,4-dihydropyridin- 4-yl)phenoxy)acetamide) by acid-catalyzed condensation of the bis-aldehydes with four equivalents of 3-aminocrotononitrile was reported. Results: The structures of the synthesized compounds were confirmed by different spectral tools. The molecular docking stimulation studies indicated that the prepared compounds bind to the active site of cellular inhibitor apoptotic protein (cIAP1-BIR3). MTT assay for the novel bis(1,4-dihydropyridines) was performed on two different human cell lines (A549 and HCT116). Conclusion: Compound 5a showed higher cytotoxic activity against A549. Compound 5d showed moderate activity against HCT116. The rest of compounds indicated lower or no activity against both cell lines.