Medicinal Chemistry

Heterocycles are very important functional groups, especially in medicinal chemistry. They are not only pivotal in the synthesis of drugs, but also form part of the structure of a diversity of drugs, vitamins, natural products and biomolecules. The importance of azolines and imidazoles in heterocycles lies in the fact that their derivatives are known for analgesic, antifungal, antihypertensive, antiobesity, anticancer, and other biological activity. Additionally, they can inhibit butyrylcholinesterase, acetylcholinesterase, carboxylesterase and quorum sensing. Due to these properties, the present contribution reviews the use of azoline and imidazole moieties in recent drug synthesis based on classic as well as non-classic methods, the latter employing microwave and sonication energies. Also included is the preparation from oxazoline of nanostructured material having biomedical applications. Hence, the present focus is on the synthesis of azolines and imidazoles that are directly involved in the preparation of drug precursors and potential drugs.

Colchicine irreversibly binds to tubulin, blocks microtubule formation, and inhibits cell division. However, its usage as an antitumor agent is limited due to its distribution to many tissues and low accumulation in the tumor. The increase in molecule weight can change colchicine biodistribution and decrease side effects. The aim of this work was to study in vivo and in vitro antitumor activity of colchicine-chitosan conjugate. A new allocolchicine derivative – furanoallocolchicinoid 3 was synthesized and conjugated to chitosan (4). Both 3 and 4 induced in vitro tubulin reorganization, cell cycle arrest, and inhibition of cell proliferation in 2D and 3D cultures. Antitumor effect of chitosan, 3, and 4 was studied in Wnt-1 breast tumor bearing mice. Conjugate 4 demonstrated significantly better tumor growth inhibition than 3 possibly as a result of a better accumulation in the tumor.

Moringa oleifera is a kind of woody tree traditionally used as a nutritional source and as a medicinal plant. It grows wild in the tropical and subtropical areas of Asia, Africa and the Middle East. In China, Moringa oleifera trees are planted at a large scale in Yunnan, Guangdong and Guangxi Provinces. As a nutritional and medicinal plant, Moringa oleiferais a rich source of bioactive compounds with diverse pharmacological activities. It has been widely used in the treatment of certain diseases as a traditional medicinal herb. Antimicrobial activity is the most studied property of Moringa oleifera. Many studies have shown that the leaf, flower, bark, root, seed, and nearly all types of Moringa oleiferatissues exhibit antimicrobial activity including antibacterial, antifungal, antiviral and antiparasitic activity. This review describes progress on research conducted to understand the antimicrobial activity and related bioactive properties of Moringa oleifera compounds, and discusses the potential use of Moringa oleiferain the control of pathogenic microbes.

In the course of studies directed towards the synthesis of novel AChE and BChE inhibitors, for the treatment of Alzheimer disease, we focused on the conventional versus microwave assisted synthesis of seventeen benzohydrazide derivatives and tested their ability as AChE and BChE inhibitors. These derivatives were characterized by FT-IR, 1H-NMR, 13C-NMR and EI-MS. Seventeen derivatives exhibited varied acetylcholinesterase inhibition with IC50 values ranging between 72.04 ± 1.12 to 1320.65 ± 0.95 μM as well as butyrylcholinesterase activity with IC50 values ranging between 3.04 ± 1.48-1876.17 ± 0.95 μM as compared with standard eserine (IC50=0.85 ± 0.0001 μM). Only two analogs 3k and 3o exhibited moderate acetylcholinesterase inhibitor potential with IC50 values 72.04 ± 1.12 and 94.06 ± 1.17 μM respectively. Five analogs 3d, 3h, 3q, 3o and 3l exhibited good potent butyrylcholinesterase inhibitory potential with IC50 values 3.04 ± 1.48, 9.01 ± 0.58, 15.12 ± 0.66, 45.00 ± 0.99 and 50.19 ± 0.62 μM respectively. Molecular docking studies were carried out in order to find out the binding affinity of benzohydrazide derivatives with the enzyme.

A new series of 2-substituted-3-allyl-4(3H)-quinazolinone derivatives (4a-e-8a-d) were synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)-induced seizures and maximal electroshock test in mice and compared with the reference drugs methaqualone and sodium valproate. The neurotoxicity was assessed using rotarod test. The molecular modeling was performed for all synthesized compounds to predict their binding affinity towards GABA-A receptor as a proposed mode of their anticonvulsant activity. The data obtained from the molecular docking was strongly correlated with that obtained from the biological screening which revealed that; compounds 4c, 4b and 4d showed the highest binding affinities towards GABA-A receptor and also showed the highest anticonvulsant activities in experimental mice with relatively low neurotoxicity and low toxicity in the median lethal dose test when compared with the reference drugs. The obtained results proved that the most active compounds could be useful as a model for future design, adaptation and investigation to construct more active analogs.