Current Topics in Medicinal Chemistry - Volume 23, Issue 11, 2023

Medicinal and aromatic plants are known to have a number of biologically active compounds. Since ancient times, such plants have been used in ethnopharmacology. A number of medicines have been developed from plant origin by researchers and researchers continue to be interested in plant-based medicines. Zingiberaceae is a well-known plant family for such types of medicinal and aromatic plants. Zingiber is the third largest genus of this family and Zingiber roseum (Roxb.) Roscoe is a medicinal and aromatic Z. roseum is a rhizomatous perennial herbaceous plant of this genus, popularly known as “Rosy Ginger” and “Jangli Adrak,” utilized in the Siddha arrangement of medication, and its rhizomes have been used to treat injury, cough, asthma, skin illnesses, gastric ulcers, liver diseases, and heartburn in tradition. It also has ethnopharmacological uses, such as the rhizome of Z. roseum is used for digestion, relieving giddiness, and as a stimulant. Apart from this, it has been reported for several pharmacological activities such as antispasmodic, hepatoprotective, antimicrobial, and anticancer activities, etc. Z. roseum is a reservoir of several chemical constituents such as terpenes and terpenoids such as linalool, α-pinene, β-pinene, limonene, terpinen-4-ol, α- terpineol, etc., phenols, flavonoids, alkaloids, saponins, and ascorbic acid along with important unique constituents such as zerumbone which are responsible for its medicinal and other biological activities. In this review article, we discussed the thorough knowledge published by researchers regarding the phytochemistry, ethnopharmacological, and mediational properties of Z. roseum and its botanical descriptions.

Background: Effective cancer treatment still challenges medicine since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm, and the outcome of patients, especially those with advanced castration-resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as docetaxel (DOC). Objectives: This study investigated the synergistic potentiation of 4-nerolidylcatechol (4-NC) with DOC in inhibiting androgen-independent PCa cells. Methods: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT). Results: 4-NC significantly reduced the viability of PC-3 cells in a dose-dependent manner, decreasing colony formation and proliferation. The combination of 4-NC and DOC was synergistic in the androgen-independent cells and allowed the reduction of DOC concentration, with increased cytotoxicity and induction of apoptosis when compared to compounds alone. Furthermore, when 4- NC was co-administered with DOC, higher expression levels of proteins associated with the epithelial phenotype were observed, controlling EMT in PC-3 cells. Conclusion: Collectively, these data demonstrated, for the first time, that the combination of 4-NC with reduced doses of DOC could be especially valuable in the suppression of oncogenic mechanisms of androgen-independent PCa cells.

Pharmaceutical chemistry has many industrial processes that must be studied and adapted to a new reality where the environment must be the focus of all production chains. Thus, new technologies that are cleaner and use renewable sources of raw materials still need to be developed and applied to materials that go to the market, and they need to reach a level that is less harmful to the environment. This applies especially in areas related to the pharmaceutical industries since chemical products are used in the production of medicines and used in many other areas of everyday life and are included in the Sustainable Development Goals proposed by the United Nations. This article intends to provide insight into some relevant topics that can stimulate researchers toward medicinal chemistry that can contribute to a sustainable future of the biosphere. This article is structured around four interconnected themes that influence how green chemistry can be important for a future where science, technology and innovation are key to mitigating climate change and increasing global sustainability.

Over the last two decades, with the advent of continuous flow technologies, continuous processes have emerged as a major area in organic synthesis. In this context, continuous flow processes have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development of multi-step protocols has attracted special interest from the academic and industrial chemistry communities. In addition to the beneficial aspects intrinsically associated with continuous processes (e.g., waste reduction, optimal heat transfer, improved safety, and the possibility to work under harsh reaction conditions and with more dangerous reagents), these protocols also allow a rapid increase in molecular complexity. Moreover, in telescoped multi-step processes, isolation and purification steps are generally avoided or, if necessary, carried out in-line, presenting an important economy of time, solvents, reagents, and labor. Last, important synthetic strategies such as photochemical and electrochemical reactions are compatible with flow processes and are delivering relevant advances to the synthetic approaches. In this review, a general overview of the fundamentals of continuous flow processes is presented. Recent examples of multi-step continuous processes for the preparation of fine chemicals, including telescoped and end-to-end processes, are discussed, pointing out the possible advantages and/or limitations of each of these methodologies.

Multicomponent reactions (MCRs) are processes in which three or more starting materials are combined in the same reaction vessel, forming an adduct that contains all or most of the atoms of the starting materials. MCRs are one-pot processes that provide attractive advantages for the total synthesis of target molecules. These reactions allow rapid access to structurally complex adducts from particularly simple starting materials. Moreover, MCRs are generally intrinsically associated with principles of green syntheses, such as atom economy, minimization of isolation, and purification of synthetic intermediates, leading to large solvent economies and avoiding the production of large amounts of reaction waste. Thus, synthetic routes employing multicomponent reactions are generally more convergent, economical and often allow higher overall yields. In total synthesis, the use of MCRs has been mainly applied in the preparation of key advanced intermediates. Progress in the use of MCRs in total synthesis has been described over the last decades, including not only classical MCRs reactions (e.g. isocyanide-based transformations), but also non-traditional multicomponent reactions. Furthermore, reports concerning stereoselective multicomponent transformations are still scarce and present further development opportunities. This review aims to provide a general overview of the application of MCRs as key steps in the rapid preparation of structurally complex derivatives and fine chemicals. In special, some selected examples have been successfully applied for medicinal purposes. Finally, in some representative cases, either key intermediates formed during the reaction vessel or corresponding transition states have been disclosed in order to provide insights into the reaction mechanisms.

Neglected tropical diseases (NTDs) affect mainly poor and marginalized populations of tropical and subtropical areas in 150 countries. Many of the chemical processes involved in the synthesis of active pharmaceutical ingredients (APIs) are highly polluting and inefficient, both in terms of materials and energy-consuming. In this review, we present the green protocols developed in the last 10 years to access new small molecules with potential applications in the treatment of leishmania, tuberculosis, malaria, and Chagas disease. The use of alternative and efficient energy sources, like microwaves and ultrasound, as well as reactions using green solvents and solvent-free protocols, are discussed in this review.