Combination Therapies of Artemisinin and its Derivatives as a Viable Approach for Future Cancer Treatment

Abstract

Background: Many anticancer drugs have been developed for clinical usage till now, but the major problem is the development of drug-resistance over a period of time in the treatment of cancer. Anticancer drugs produce huge adverse effects, ultimately leading to death of the patient. Researchers have been focusing on the development of novel molecules with higher efficacy and lower toxicity; the anti-malarial drug artemisinin and its derivatives have exhibited cytotoxic effects. Methods: We have done extensive literature search for artemisinin for its new role as anti-cancer agent for future treatment. Last two decades papers were referred for deep understanding to strengthen its role. Results: Literature shows changes at 9, 10 position in the artemisinin structure produces anticancer activity. Artemisinin shows anticancer activity in leukemia, hepatocellular carcinoma, colorectal and breast cancer cell lines. Artemisinin and its derivatives have been studied as combination therapy with several synthetic compounds, RNA interfaces, recombinant proteins and antibodies etc., for synergizing the effect of these drugs. They produce an anticancer effect by causing cell cycle arrest, regulating signaling in apoptosis, angiogenesis and cytotoxicity activity on the steroid receptors. Many novel formulations of artemisinin are being developed in the form of carbon nanotubes, polymer-coated drug particles, etc., for delivering artemisinin, since it has poor water/ oil solubility and is chemically unstable. Conclusion: We have summarize the combination therapies of artemisinin and its derivatives with other anticancer drugs and also focussed on recent developments of different drug delivery systems in the last 10 years. Various reports and clinical trials of artemisinin type drugs indicated selective cytotoxicity along with minimal toxicity thus projecting them as promising anti-cancer agents in future cancer therapies.

Alleviating Catalyst Decay Enables Efficient Intermolecular C(sp3)–H Amination under Mechanochemical Conditions

“…Rapid formation of aminated celestolide 3y (85%) and retinoic acid receptor agonist analogue 3z (80%) was also observed. Artemisinin, , a renowned active pharmaceutical ingredient (API) for its potent antimalarial activity bearing an unusual peroxide bridge, was selectively functionalized at the C7 position among additional six potential oxidation sites. The conversion was relatively low with a substantial amount of starting materials recovered.…”

The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer

“…ART has very promising clinical applications. ART acts not only on tumor cells alone in experiments but also in combination with a variety of drugs, including radiotherapy, natural products, photodynamic therapy, and recombinant proteins [ 16 , 17 ]. Some researchers have accurately used exosomes and nanoparticles as tools to induce ferroptosis in tumor cells [ 117 ].…”

“…ARTs also exhibit the following anticancer functions: cell cycle arrest [9], suppression of angiogenesis [10], inhibition of cell metastasis and invasion [11], DNA damage [12][13][14], and ferroptosis. ART-type drugs could be applied in combination with other therapeutic modalities in clinical oncology and can inhibit tumor growth in different ways, making them attractive chemotherapeutic agents for cancer treatment [15][16][17]. Dixon et al in 2012 [18] and is characterized by the accumulation of lipid peroxidation and iron, the effects of which can be inhibited by iron chelators [19].…”

Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones

“…Currently, the MDR of oncolytic agents has limited the efficient treatment of many types of cancer, so combination chemotherapy with more than one molecular target is a promising approach to overcome this problem, as evidenced by ART and several of its derivatives. 31 Thus, a number of ARTestrogen hybrids have been synthesized, and they all exhibited cytotoxicity against human MCF-7, MDA-MB-231, MDA-MB-361, and T47D breast and C33A cervical cancer cells, with the activity improved around 10-fold when compared with their respective parent compounds. Of these, benzylestrondiol-ART nonacetal hybrid (1e) was the most potent, showing IC 50 values of 0.45, 0.86, and 0.15 μM against MCF-7, MDA-MB-231, and C33A cells, respectively (Figure 1), indicating that hybridization of ART may have translational potential for developing innovative anticancer agents.…”