Discovery of Anticancer Agents of Diverse Natural Origin

Abstract

Research progress from mainly over the last five years is described for a multidisciplinary collaborative program project directed toward the discovery of potential anticancer agents from a broad range of taxonomically defined organisms. Selected lead compounds with potential as new antitumor agents that are representative of considerable structural diversity have continued to be obtained from each of tropical plants, terrestrial and aquatic cyanobacteria, and filamentous fungi. Recently, a new focus has been on the investigation of the constituents of U.S. lichens and their fungal mycobionts. A medicinal chemistry and pharmacokinetics component of the project has optimized structurally selected lead natural products, leading to enhanced cytotoxic potencies against selected cancer cell lines. Biological testing has shown several compounds to have in vivo activity, and relevant preliminary structure−activity relationship and mechanism of action studies have been performed. Several promising lead compounds worthy of further investigation have been identified from the most recent collaborative work performed.

Drugs That Changed Society: Microtubule-Targeting Agents Belonging to Taxanoids, Macrolides and Non-Ribosomal Peptides

“…The present review emphasizes the chemistry of the taxanoids and the clinical progressions obtained by introduction of new semisynthetic analogues. New sources for natural products have led to macrolides and peptides which may improve the possibilities for treatment of cancer diseases [ 11 ].…”

Molecular-docking-guided design, palladium-catalyzed synthesis and anticancer activity of paclitaxel-benzoxazoles hybrids

“…Although many effective approaches including radiation, surgery and targeted therapy have been exploited to cure for cancer, natural products or its derivatives have been of particular interest as cancer chemotherapeutic agents in the past few decades. Up to date, more than 100 anticancer agents with varied mechanisms of action have been developed from diverse natural origin 4 – 6 . Paclitaxel (Taxol ® ), the naturally diterpenoid extract from the bark of Taxus brevifolia Nutt, and the semisynthetic analogues docetaxel (Taxotere®) and cabazitaxel (Jevana®) (Fig.…”

Embellicines C-E: Macrocyclic Alkaloids with a Cyclopenta[b]fluorene Ring System from the Fungus Sarocladium sp.

“…(fungal strain MSX6737), which exhibited cytotoxic activity against human melanoma, breast, and ovarian cancer cells when tested at a concentration of 20 μg/mL (i.e., less than 40% cancer cell survival relative to a negative control). 32 The structures were determined by examining their one-dimensional (1D) and two-dimensional (2D) NMR data. In addition, nuclear Overhauser effect spectroscopy (NOESY) spectra, along with the experimental and calculated ECD spectra, were used to assign their relative and absolute configurations.…”

“…In the course of ongoing studies to discover fungal metabolites with potent cytotoxic activities, − we report the characterization of a series of embellicines ( 1 – 5 ), including the isolation of the known embellicine A ( 1 ), three new embellicines C, D, and E ( 2 , 4 , and 5 , respectively), and the semisynthetic generation of the acetylated analogue, 2′- O -acetyl-embellicine C ( 3 ). These macrocyclic alkaloids with a cyclopenta­[b]­fluorene ring system were obtained from the organic extract of a Sarocladium sp.…”

“…These macrocyclic alkaloids with a cyclopenta­[b]­fluorene ring system were obtained from the organic extract of a Sarocladium sp. (fungal strain MSX6737), which exhibited cytotoxic activity against human melanoma, breast, and ovarian cancer cells when tested at a concentration of 20 μg/mL (i.e., less than 40% cancer cell survival relative to a negative control) . The structures were determined by examining their one-dimensional (1D) and two-dimensional (2D) NMR data.…”