Letters in Drug Design & Discovery - Volume 17, Issue 5, 2020

Background: Natural occurring β-Carbolines alkaloids are abundant in the plant kingdom or other organisms, and they were found to possess good antitumor activity through multiple mechanisms. Based on previous summarized SARs of β-carboline derivatives, the modification on pyridine ring would have a great impact on their antitumor activities. Therefore, we plan to synthesized arylated β-carboline-3-amides to find more v Read More

Background: Oxime compounds, including oxime ethers and oxime esters, possess various biological activities. Many oxime ethers have been widely used in the fields of pesticides and medicines. However, oxime ethers are rarely used in the field of pesticides. Methods: We chose the excellent fungicide pyrifenox as the lead compound, integrated pyridinyl, adamantyl and benzoyl moieties into one molecule, while also Read More

Background: Diabetes is the foremost health problem worldwide predisposing to increased mortality and morbidity. The available synthetic drugs have serious side effects and thus, emphasize further need to develop effective medication therapy. GPR40 represents an interesting target for developing novel antidiabetic drug. In the current study, searching of potential natural hit candidate as agonist by using structure based Read More

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin, indomethacin, flufenamic acid and phenylbutazone are used to treat most of the inflammatory disorders. These NSAIDs are also associated with serious side effects including gastric ulceration, nephrotoxicity, and bleeding, mainly due to acidic nature. Hence, there is a need to identify highly potent and safer treatment for inflam Read More

Background: Biological system complexity impedes the drug target identification by biological experiments. Thus drugs, rather than acting on target site only, can interact with the entire biological system. Study of this phenomenon, known as network pharmacology, provides grounds for biological target identification of new drugs or acts as a foundation for the discovery of new targets of present drugs. No publication is a Read More

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and a Read More

Background: Pyrazolines, electron-rich nitrogen carriers, are of great importance due to their potential applications for the treatment of many diseases including inflammation, infectious diseases and neurodegenerative disorders. Objectives: The purpose of this work was to synthesize new pyrazoline derivatives and evaluate their anticholinesterase effects. Methods: 1-Aryl-5-[4-(piperidin-1-yl)phenyl]-3-(3,4-dimethoxyphenyl) Read More

Background: FMS-like tyrosine kinase-3 (FLT3) belongs to the class III Receptor Tyrosine Kinase (RTK) family. FLT3 is involved in normal hematopoiesis and is generally expressed in early hematopoietic progenitor cells. Mutations either with an internal tandem duplication of FMS-like tyrosine kinase-3 (FLT3-ITD) or point mutation at the activation loop leads to the Acute Myeloid Leukemia (AML), a highly heterogeneous Read More

Background: A wide range of thiazole, pyrazole and pyran derivatives gained special attention due to pharmacological activities especially therapeutic activities. Many pharmacological drugs containing the thiazole and pyrazole nuclei are known in the market. Methods: The 2-arylidencyclohexan-1,3-dione 3a-c were the key starting compounds for many heterocyclic reactions to produce substituted heterocyclic Read More

Background: Considering that AD is multifactorial in nature, novel series of imidazo [2,1-b][1,3,4] thiadiazole derivatives were designed to address the basic factors responsible for the disease. Methods: These compounds were investigated as inhibitors of beta-site APP cleaving enzyme 1, acetylcholinesterase and butyryl cholinesterase. Results: The BACE1 inhibitory results indicated that nitro phenyl substituted derivatives Read More

Introduction: G protein-coupled receptor kinase 2 (GRK2) is known to be implicated in heart failure, and therefore serves as an important drug target. GRK2 belongs to the protein kinase A, G, and C family and shares high sequence similarity with its closely related protein, the Rhoassociated coiled-coil protein kinase 2 (ROCK2). Therefore, selective inhibition of GRK2 over ROCK2 is considered crucial for heart failure therapy. O Read More

Background: Bubonic plague is amongst the diseases with the highest potential for being used in biological warfare attacks today. This disease, caused by the bacterium Yersina pestis, is highly infectious and can achieve 100% of fatal victims when in its most dangerous form. Besides, there is no effective vaccine, and the chemotherapy available today against plague is ineffective if not administered at the beginning of the inf Read More

Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved anticancer activity. Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the synthesized compounds 6a-x agains Read More

Background: Aromatase inhibitors emerged as a pivotal moiety to selectively block estrogen production, prevention and treatment of tumour growth in breast cancer. De novo drug design is an alternative approach to blind virtual screening for successful designing of the novel molecule against various therapeutic targets. Objective: In the present study, we have explored the de novo approach to design novel aromatase Read More

Introduction: Topoisomerase II alpha (Topo IIα) has become one of the extensively exploited targets in chemotherapy due to its role in regulating the topological constraints of DNA during replication and transcription. Small molecules targeting Topo IIα’s activity such as etoposide (VP-16) and doxorubicin are extensively used in the treatment of many different types of cancer. Objective: Here, the effects of three small molecule Read More

The pandemic spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) that causes COVID-19 calls for global health emergency with wide prevalence across 94 countries, and around 3073 deaths reported in china on 7th March 2020 which created red alert zone in the country. It was further noticed other than China, countries like the republic of Korea ranked first with 6767 cases, Italy with 4747 and Iran with 351 Read More