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Guayule (Parthenium argentatum Gray) is a semi-arid shrub, native from the Chihuahan desert. This plant produces polyisoprene and resin. Polyisoprene is the main focal point of many researches, from structure to properties. Today, some processes are used to extract polyisoprene under its dry form, using solvent extraction, to produce rubber (used in truck or airplane tires) or as an emulsion, to make latex products by dipping (used in medical gloves, condoms, etc.). This article focuses on guayule resin which has some interesting applications in adhesives, coatings, pharmaceuticals, etc. In order to better know the resin composition and to be able to perform comparisons between varieties or seasons, liquid and gas chromatographic analysis methods have been described, for the groups of molecules composing the resin (polyphenols, guayulins, free fatty acids, di and triacylglycerols, argentatins, alkanes, alkanals, sugars, organic acids). Unlike other articles, this study aims to analyze all components of the same resin; the average composition of a guayule resin is given., (© 2023. The Author(s).)

Natural rubber is an essential material, especially for plane and truck tyres but also for medical gloves. Asia ranks first in the production of natural rubber, of which the Hevea tree is currently the sole source. However, it is anticipated that this source alone will not be able to fulfill the growing demand. Guayule, a shrub native to northern Mexico and southern United States, may also contribute. This plant not only contains polyisoprene, but also resin, a mixture of lipids and terpenoids. This review summarizes various aspects of this plant, from the usage history, botanical description, geographical distribution and cultivation practices, down to polyisoprene and resin biosynthesis including their distribution within the plant and molecular composition. Finally, the main processes yielding dry rubber or latex are depicted, as well as the properties of the various extracts along with economic considerations. The aim is to provide a wide picture of current knowledge available about this promising crop, a good feedstock candidate for a multiple-product biorefinery.

The PI3K pathway is considered a master regulator for cancer due to its frequent activation, making it an attractive target for pharmacologic intervention. While substantial efforts have been made to develop drugs targeting PI3K signaling, few drugs have been able to achieve the inhibition necessary for effective tumor control at tolerated doses. HSP90 is a chaperone protein that is overexpressed and activated in many tumors and as a consequence, small-molecule ligands of HSP90 are preferentially retained in tumors up to 20 times longer than in normal tissue. We hypothesize that the generation of conjugates that use a HSP90-targeting ligand and a payload such as copanlisib, may open the narrow therapeutic window of this and other PI3K inhibitors. In support of this hypothesis, we have generated a HSP90-PI3K drug conjugate, T-2143 and utilizing xenograft models, demonstrate rapid and sustained tumor accumulation of the conjugate, deep pathway inhibition, and superior efficacy than the PI3K inhibitor on its own. Selective delivery of T-2143 and the masking of the inhibitor active site was also able to mitigate a potentially dose-limiting side effect of copanlisib, hyperglycemia. These data demonstrate that by leveraging the preferential accumulation of HSP90-targeting ligands in tumors, we can selectively deliver a PI3K inhibitor leading to efficacy in multiple tumor models without hyperglycemia in mice. These data highlight a novel drug delivery strategy that allows for the potential opening of a narrow therapeutic window through specific tumor delivery of anticancer payloads and reduction of toxicity., (©2020 American Association for Cancer Research.)

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a 95% mortality rate with no improvement to treatment in decades, and new therapies are desperately needed. PEN-221 is a miniaturized peptide-drug conjugate (∼2 kDa) designed to target SCLC via a Somatostatin Receptor 2 (SSTR2)-targeting ligand and to overcome the high proliferation rate characteristic of this disease by using the potent cytotoxic payload, DM1. SSTR2 is an ideal target for a drug conjugate, as it is overexpressed in SCLC with limited normal tissue expression. In vitro , PEN-221 treatment of SSTR2-positive cells resulted in PEN-221 internalization and receptor-dependent inhibition of cellular proliferation. In vivo , PEN-221 exhibited rapid accumulation in SSTR2-positive SCLC xenograft tumors with quick clearance from plasma. Tumor accumulation was sustained, resulting in durable pharmacodynamic changes throughout the tumor, as evidenced by increases in the mitotic marker of G 2 -M arrest, phosphohistone H3, and increases in the apoptotic marker, cleaved caspase-3. PEN-221 treatment resulted in significant antitumor activity, including complete regressions in SSTR2-positive SCLC xenograft mouse models. Treatment was effective using a variety of dosing schedules and at doses below the MTD, suggesting flexibility of dosing schedule and potential for a large therapeutic window in the clinic. The unique attributes of the miniaturized drug conjugate allowed for deep tumor penetration and limited plasma exposure that may enable long-term dosing, resulting in durable tumor control. Collectively, these data suggest potential for antitumor activity of PEN-221 in patients with SSTR2-positive SCLC., (©2019 American Association for Cancer Research.)

In recent years, almost all extraction processes in the perfume, cosmetic, pharmaceutical, food ingredients, nutraceuticals, biofuel and fine chemical industries rely massively on solvents, the majority of which have petroleum origins. The intricate processing steps involved in the industrial extraction cycle makes it increasingly difficult to predict the overall environmental impact; despite the tremendous energy consumption and the substantial usage of solvents, often the yields are indicated in decimals. The ideal alternative solvents suitable for green extraction should have high solvency, high flash points with low toxicity and low environmental impacts, be easily biodegradable, obtained from renewable (non-petrochemical) resources at a reasonable price and should be easy to recycle without any deleterious effect to the environment. Finding the perfect solvent that meets all the aforementioned requirements is a challenging task, thus the decision for the optimum solvent will always be a compromise depending on the process, the plant and the target molecules. The objective of this comprehensive review is to furnish a vivid picture of current knowledge on alternative, green solvents used in laboratories and industries alike for the extraction of natural products focusing on original methods, innovation, protocols, and development of safe products., Competing Interests: The authors declare no conflict of interest.

Somatostatin receptor 2 (SSTR2) is frequently overexpressed on several types of solid tumors, including neuroendocrine tumors and small-cell lung cancer. Peptide agonists of SSTR2 are rapidly internalized upon binding to the receptor and linking a toxic payload to an SSTR2 agonist is a potential method to kill SSTR2-expressing tumor cells. Herein, we describe our efforts towards an efficacious SSTR2-targeting cytotoxic conjugate; examination of different SSTR2-targeting ligands, conjugation sites, and payloads led to the discovery of 22 (PEN-221), a conjugate consisting of microtubule-targeting agent DM1 linked to the C-terminal side chain of Tyr 3 -octreotate. PEN-221 demonstrates in vitro activity which is both potent (IC 50 = 10 nM) and receptor-dependent (IC 50 shifts 90-fold upon receptor blockade). PEN-221 targets high levels of DM1 to SSTR2-expressing xenograft tumors, which has led to tumor regressions in several SSTR2-expressing xenograft mouse models. The safety and efficacy of PEN-221 is currently under evaluation in human clinical trials.

Dysregulation of Notch signaling has been implicated in the development of many different types of cancer. Notch inhibitors are being tested in the clinic, but in most cases gastrointestinal and other toxicities have limited the dosage and, therefore, the effectiveness of these therapies. Herein, we describe the generation of a monoclonal antibody against the ligand-binding domain of the Notch1 receptor that specifically blocks ligand-induced activation. This antibody, 23814, recognizes both human and murine Notch1 with similar affinity, enabling examination of the effects on both tumor and host tissue in preclinical models. 23814 blocked Notch1 function in vivo, inhibited functional angiogenesis, and inhibited tumor growth without causing gastrointestinal toxicity. The lack of toxicity allowed for combination of 23814 and the VEGFR inhibitor tivozanib, resulting in significant growth inhibition of several VEGFR inhibitor-resistant tumor models. Analysis of the gene expression profiles of an extensive collection of murine breast tumors enabled the successful prediction of which tumors were most likely to respond to the combination of 23814 and tivozanib. Therefore, the use of a specific Notch1 antibody that does not induce significant toxicity may allow combination treatment with angiogenesis inhibitors or other targeted agents to achieve enhanced therapeutic benefit., (©2015 American Association for Cancer Research.)

This paper describes a portable microwave assisted extraction apparatus (PMAE) for extraction of bioactive compounds especially essential oils and aromas directly in a crop or in a forest. The developed procedure, based on the concept of green analytical chemistry, is appropriate to obtain direct in-field information about the level of essential oils in natural samples and to illustrate green chemical lesson and research. The efficiency of this experiment was validated for the extraction of essential oil of rosemary directly in a crop and allows obtaining a quantitative information on the content of essential oil, which was similar to that obtained by conventional methods in the laboratory., (Copyright © 2013 Elsevier B.V. All rights reserved.)

One of the principal objectives of sustainable and green processing development remains the dissemination and teaching of green chemistry in colleges, high schools, and academic laboratories. This paper describes simple glassware that illustrates the phenomenon of extraction in a conventional microwave oven as energy source and a process for green analytical chemistry. Simple glassware comprising a Dean-Stark apparatus (for extraction of aromatic plant material and recovery of essential oils and distilled water) and a Vigreux column (as an air-cooled condenser inside the microwave oven) was designed as an in-situ extraction vessel inside a microwave oven. The efficiency of this experiment was validated for extraction of essential oils from 30 g fresh orange peel, a by-product in the production of orange juice. Every laboratory throughout the world can use this equipment. The microwave power is 100 W and the irradiation time 15 min. The method is performed at atmospheric pressure without added solvent or water and furnishes essential oils similar to those obtained by conventional hydro or steam distillation. By use of GC-MS, 22 compounds in orange peel were separated and identified; the main compounds were limonene (72.1%), β-pinene (8.4%), and γ-terpinene (6.9%). This procedure is appropriate for the teaching laboratory, does not require any special microwave equipment, and enables the students to learn the skills of extraction, and chromatographic and spectroscopic analysis. They are also exposed to a dramatic visual example of rapid, sustainable, and green extraction of an essential oil, and are introduced to successful sustainable and green analytical chemistry.

Structural characterization of membrane proteins is hampered by the instability of the isolated proteins in detergent solutions. Here, we describe a new class of phospholipid-like surfactants that stabilize the G protein-coupled receptor, BLT1. These compounds, called C(13)U(9), C(13)U(19), C(15)U(25) and C(17)U(16), were synthesized by radical polymerization of Tris(hydroxymethyl) acrylamidomethane in the presence of thioglycerol, first endowed with two hydrocarbon chains with variable lengths (13-17 carbon atoms), as transfer reagent. C(13)U(19), C(17)U(16) or C(15)U(25) significantly enhanced the stability of BLT1 in solution compared to what was obtained with common detergents. These molecules therefore represent a promising step towards the structural characterization of BLT1 and possibly other membrane proteins.