Semisynthetic and newly designed derivatives based on natural chemical scaffolds: moving beyond natural products to fight Trypanosoma cruzi

Marine alkaloids as bioactive agents against protozoal neglected tropical diseases and malaria

“…51 5 also prolonged the survival of treated animals by promoting the production of specic antibodies (IgG) against the Plasmodium parasite. Manzamine alkaloids were also isolated from the sponge Acanthostronglyophora sp., namely manzamine J (12), manzamine A N-oxide (13), ircinal A ( 14), ircinol A (15), 6hydroxymanzamine E ( 16) and neo-kauluamine (17). These presented leishmanicidal activity against L. donovani promastigotes with IC 50 values of 0.9-25.0 mg mL À1 , and CC 50 values ranging from 1.1 mg mL À1 to non-cytotoxic concentrations (CC 50 >4.7 mg mL À1 ).…”

“…14,15 Traditionally regarded as non-viable for such purposes due to synthetic intractability, low natural abundance, polypharmacology, and inexibility with respect to analogue synthesis, advances in synthetic organic chemistry offer a realistic means to access and diversify such scaffolds. 16,17 This review focuses on alkaloids isolated from the marine environment, which have long been recognised as a low-abundance but high-potential source of bioactive agents. Following a discussion of the existing state of the art with respect to the diseases and their treatments, those marine alkaloids that have been evaluated for antiprotozoal bioactivity in the period 2000-2020 are described, with an emphasis on the most potent isolates.…”

Phytochemical conjugation as a potential semisynthetic approach toward reactive and reuse of obsolete sulfonamides against pathogenic bacteria

“…Sometimes, isolation and utilization of individual phytoconstituents in mainstream medicine is a challenging task; nevertheless, phytochemicals are more conventional, suitable, alternative, and lesser toxic sources for future drug discovery (Ahmad & Aqil, 2007; Amaral et al, 2011; Cao et al, 2017; Shirwaikar et al, 2013; Swain & Padhy, 2015). Furthermore, progress through novel techniques and instrumentations in the field novel phytochemical isolation and characterization, as well as further modification and conjugation through the principles of medicinal chemistry, are substantially essential in the development of novel therapeutics (da Rosa, Schenkel, & Bernards, 2020; Dias, Urban, & Roessner, 2012; Jayaraman et al, 2013; Swain, Paidesetty, & Padhy, 2020; WHO, 2013).…”

“…However, resistance to newer antibacterials is an ongoing process in standard microbial consortia in nature, for the natural existence against environmental factors. On the other hand, toward controlling those notorious microbial communities, humans always try to develop such potential therapeutic agents by utilizing natural resources (da Rosa et al, 2020; Swain et al, 2019; Yao et al, 2017). Indeed, the molecular biology, genomics, and proteomics facts with pharmaceutical sciences have significant contributions in newer lead‐drug discovery from phytoextracts.…”

Synthesis and Structure–Activity Relationship of Dehydrodieugenol B Neolignans against Trypanosoma cruzi

“…Natural products are a proven source of drugs, either in their natural form, as synthetic/semisynthetic derivatives, or as a basic pharmacophore. 11 Parasitic diseases are no exception, 12 − 15 with the frontline treatments for malaria (artemisinin) and visceral leishmaniasis (amphotericin B and paromomycin) themselves being natural products. 16 , 17 As part of a program to identify new antitrypanosomal agents, we previously reported the isolation of dehydrodieugenol B ( 1 , Figure 1 ) and methyl dehydrodieugenol B ( 2 ) from the plant Nectandra leucantha and their bioactivity against T. cruzi .…”