Mini Reviews in Medicinal Chemistry - Volume 18, Issue 10, 2018

Glycosidases have important anti-cancer, anti-viral and anti-diabetic properties. This review covers the literature in the past 15 years since our initial review in this journal on “neutral” glycosidase inhibitors lacking a basic nitrogen found in iminosugars and azasugars or inhibitors that are neutral by virtue of being “charge-balanced” (zwitterionic). These structurally diverse inhibitors include lactones, lactams, epoxides such as cyclophellitol, and sulfonium ion derivatives of the natural product salacinol. Synthetic efforts toward cyclophillitol, salicinol and derivatives are also highlighted. Importantly, certain metals can inhibit glycosidases and care must be taken to remove residual catalysts from synthetic material to be tested against these enzymes.

The 3,4-dihydro-2(1H)-quinolinone moiety is present in a number of pharmacologically active compounds. These include FDA approved drugs such as cilostazol, carteolol and aripiprazole as well as numerous experimental compounds. Compounds containing the 3,4-dihydro-2(1H)-quinolinone moiety also exhibit a variety of activities in both the peripheral and central tissues, which includes phosphodiesterase inhibition, blocking of β-adrenergic receptors, antagonism of vasopressin receptors and interaction with serotonin and dopamine receptors. Based on its versatility in drug design and action, this paper reviews the pharmacological actions of compounds containing the 3,4-dihydro-2(1H)- quinolinone scaffold with emphasis being placed on the most important and significant members of each activity class.

Background: Esterase is an enzyme that splits esters into an acid and alcohol. Varieties of esterases are present in human body to control diverse set of cellular processes and execute their specific functions. It can be seen that any increase in metabolites produced by these enzymes lead to severe pathological conditions like Alzheimer disease, hypercholesterolemia etc. Objective: Numerous esterase inhibitors have been developed and reported by the researchers around the globe, but not systematically summarized yet. Therefore, this assemblage focuses on various reported esterase inhibitors during recent past with detailed account of the design strategies employed for the synthesis of novel drug entities. The article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of inhibitors as esterase inhibition. The interactions with the amino acid residues responsible for esterase inhibitory potential of molecules have also been discussed. This compilation will be of great interest for the researchers working in the area of esterase inhibitors. Conclusion: Rivastigmine derivatives (44-53), tacrine-piperazine hybrid (136), coumarin-benzofuran derivative (169), coumarin-benzylpiperidine hybrid (181) and phenylcinnamide derivative (220) found to be exerting cholinesterase inhibition with IC50 below the range of 1 nM. Whereas, flavone (258) has displayed anticholesterol esterase potential below 1 nM. Benzil like derivative, (273) has also been designed and reported to possess remarkable inhibitory potential (IC50 < 1 nM) against carboxylesterase. These representative results place them in forefront as potential future drug candidates to further develop potent and specific esterase inhibitors.

Background: SnCl2·2H2O has been used as a convenient precatalyst for the one-pot and rapid synthesis of 2-substituted quinolines under ultrasound irradiation in water. The reaction involved a 3-component reaction of aniline, aldehydes, and ethyl 3,3-diethoxypropionate in the presence of aerial oxygen to give the desired products in good yields. Conclusion: Several of these compounds showed antibacterial activities when tested against gram-positive and gram-negative species. One compound i.e. 4b showed promising activities across both the species.