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Throughout history, naturally derived molecules have had countless applications in medicine, pharmacy, and biology. This rich reservoir of natural compounds demonstrated great potential in treating various diseases, mainly cancer. Alkaloids, a subfamily of secondary metabolites, are derived from a large variety of organisms including plants, animal...
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Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fi...
Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fi...
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... Several mechanisms, including DNA cleavage mediated by the inhibition of topoisomerase I & II, induction of mitochondrial permeabilization, mitotic arrest, and inhibition of enzymes, are involved in cell signaling. 60 One of the important mechanisms for the function of these compounds in cancer cells is the down-regulation of the PI3K/AKT/mTOR signaling pathway ( Figure 2). Therefore, examining their molecular aspects could open a new perspective on the use of these compounds. ...
One of the central signaling pathways with a regulatory effect on cell proliferation and survival is Akt/mTOR. In many human cancer types, for instance, lung cancer, the overexpression of Akt/mTOR has been reported. For this reason, either targeting cancer cells by synthetic or natural products affecting the Akt/mTOR pathway down-regulation is a useful strategy in cancer therapy. Direct inhibition of the signaling pathway or modulation of each related molecule could have significant feedback on the growth and proliferation of cancer cells. A variety of secondary metabolites has been identified to directly inhibit the AKT/mTOR signaling, which is important in the field of drug discovery. Naturally occurring nitrogenous and phenolic compounds can emerge as two pivotal classes of natural products possessing anticancer abilities. Herein, we have summarized the alkaloids and flavonoids for lung cancer treatment together with all the possible mechanisms of action relying on the Akt/mTOR pathway down-regulation. This review suggested that in search of new drugs, phytochemicals could be considered as promising scaffolds to be developed into efficient drugs for the treatment of cancer. In this review, the terms “Akt/mTOR”, “Alkaloid”, “flavonoid”, and “lung cancer” were searched without any limitation in search criteria in Scopus, PubMed, Web of Science, and Google scholar engines.
Keywords: Alkaloids, Cancer treatment, Drug discovery, Flavonoids, Lung cancer, PI3K/Akt/mTOR
... Plant alkaloids have long been used by humans, with their usage recorded prominently throughout ancient history and into today [88, and references therein]. The thousands of plant alkaloids currently known to exist represent a vast pharmacopeia of useful compounds that include medicines, stimulants, and many psychoactive substances [97,98]. Consequently, there is a strong incentive to produce a wide range of alkaloid compounds in microbial systems, with many recent reviews highlighting its potential to transform drug manufacture and other fields of industry [33,99,100]. ...
Plant natural products include a diverse array of compounds that play important roles in plant metabolism and physiology. After elucidation of biosynthetic pathways and regulatory factors, it has become possible to metabolically engineer new capabilities inplanta as well as successfully engineer whole pathways into microbial systems. Microbial expression systems for producing valuable plant compounds have evolved to incorporate polyculture and co-culture consortiums for carrying out robust biosynthesis strategies. This review focuses on four classes of plant secondary metabolites and the recent advances in generating useful compounds in microbial expression platforms and in plant metabolic engineering. They are the flavonoids, alkaloids, betalains, and glucosinolates.
Amine-containing drugs often show poor pharmacological properties, but these disadvantages can be overcome by using a prodrug approach involving self-immolative linkers. Accordingly, we designed l-lactate linkers as ideal candidates for amine delivery. Furthermore, we designed linkers bearing two different cargos (aniline and phenol) for preferential amine cargo release within 15 min. Since the linkers carrying secondary amine cargo showed high stability at physiological pH, we used our strategy to prepare phosphate-based prodrugs of the antibiotic Ciprofloxacin. Therefore, our study will facilitate the rational design of new and more effective drug delivery systems for amine-containing drugs.
Dehydrocrenatidine, a β-carboline alkaloid isolated from Picrasma quassioides, has been demonstrated to exert analgesic effects and play essential roles in janus kinase inhibition and exert analgesic effects through the suppression of neuronal excitability. Alkaloids such as paclitaxel and vincristine had been well explored to be chemotherapeutic agents. However, the anticancer effects of dehydrocrenatidine remain unclear. In the present study, we found that dehydrocrenatidine induced apoptosis in human oral cancer cells through both extrinsic and intrinsic pathways involving proteins such as caspase-3, caspase-8, caspase-9, poly (adenosine diphosphate-ribose) polymerase, and members of the Bcl-2 family. Cotreatment with dehydrocrenatidine and mitogen-activated protein kinase (MAPK) inhibitors indicated that dehydrocrenatidine induced apoptosis through the activation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK). The findings provide insight into the potential of dehydrocrenatidine for a new perspective on molecular regulation.
