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Historically, botanical preparations have been used to improve human health. Their active ingredients are influenced by multiple factors such as intraspecies variations, environmental conditions, collection time and methods, and the part of the plant used. To ensure the efficiency and safety of these herbal drugs, qualitative and quantitative analyses are required. A Tessaria absinthioides decoction (DETa) was reported as having hypocholesterolemic, anti-inflammatory, cytotoxic, antitumor, and antioxidative properties. This work aimed to analyze DETa by correlating its chemical composition with cytotoxic and antioxidative properties, with the aim of promoting research on it as an anticancer agent. DETa collections (2017, 2018, 2019, and 2022) were analyzed by UHPLC-DAD, UHPLC-DAD-FLD, and UPLC-MS/MS; cytotoxicity was assessed on the MCF-7 breast cancer cell line; antioxidative capacity was evaluated by the DPPH and FRAP methods; and correlation analysis was used to determine biological and chemical markers. The results provide evidence that biological activities were consistent across the collections. Among the quantified compounds, apigenin, naringin, gallocatechin gallate, ginnalin A, myricetin, epicatechin, OH-tyrosol, quercetin, and chlorogenic, tessaric, p -coumaric, vanillic, caffeic, caftaric, ellagic, and rosmarinic acids correlated as bioactive and chemical markers. Moreover, tessaric acid could be established as a species marker. Altogether, these findings add relevant information to DETa properties, encouraging further exploration of its potential application as an anticancer botanical.

Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others. The antiproliferative activity of natural sesquiterpenes, tessaric acid, ilicic acid, and ilicic alcohol and their semisynthetic derivatives against HeLa, T-47D, WiDr, A549, HBL-100, and SW1573 cell lines were evaluated. The effect of the compounds on Trypanosoma cruzi epimastigotes was also assessed. The selectivity index was calculated using murine splenocytes. Derivatives 13 and 15 were the most antiproliferative compounds, with GI50 values ranging between 5.3 (±0.32) and 14 (±0.90) μM, in all cell lines tested. The presence of 1,2,3-triazole groups in derivatives 15−19 led to improvements in activity compared to those corresponding to the starting natural product (3), with GI50 values ranging between 12 (±1.5) and 17 (±1.1) μM and 16 being the most active compound. In relation to the anti-T. cruzi activity, derivatives 7 and 16 obtained from tessaric acid and ilicic acid were among the most active and selective compounds with IC50 values of 9.3 and 8.8 µM (SI = 8.0 and 9.4), respectively.

The sesquiterpene lactones cumanin, helenalin, and hymenin and their semisynthetic derivatives were evaluated against Trypanosoma cruzi epimastigotes. The cytotoxicity of the compounds was evaluated on murine splenocytes. Cumanin diacetate was one of the most active and selective compounds [IC 50 = 3.20 ± 0.52 μg/mL, selectivity index (SI) = 26.0]. This sesquiterpene lactone was selected for its evaluation on trypomastigote and amastigote forms of the parasite. The diacetylated derivative of cumanin showed moderate activity on trypomastigotes (IC 50 = 32.4 ± 5.8 μg/mL). However, this compound was able to efficiently inhibit parasite replication with an IC 50 value of 2.2 ± 0.05 μg/mL against the amastigote forms. Cumanin diacetate showed selectivity against the intracellular forms of Trypanosoma cruzi with an SI value of 52.7. This cumanin analogue was also active on an in vivo model of Chagas disease, leading to a reduction in the parasitemia levels in comparison with nontreated animals. Histopathological analysis of skeletal muscular tissues from treated mice showed only focal interstitial lymphocyte inflammatory infiltrates with slight myocyte necrosis; in contrast, nontreated animals showed severe lymphocyte inflammatory infiltrates with necrosis of the myocytes. A molecular docking study of cumanin and its derivatives on trypanothione reductase from T. cruzi (TcTR) was performed. The results of Δ G docking achieved let the identification of diacetylated and O -alkylated derivatives of cumanin as good inhibitors of TcTR. Cumanin diacetate could be considered a potential candidate for further studies for the development of new therapies against Chagas disease., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Cancer is one of the most important causes of death worldwide. Solid tumors represent the great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturally occurring compounds that have displayed a diverse range of biological activities including cytotoxic activity. A series of oxygenated and oxy-nitrogenated derivatives ( 4 ⁻ 15 ) from the sesquiterpene lactones cumanin ( 1 ), helenalin ( 2 ), and hymenin ( 3 ) were synthesized. The silylated derivatives of helenalin, compounds 13 and 14 , were found to be the most active against tumor cell lines, with GI 50 values ranging from 0.15 to 0.59 μM. The ditriazolyl cumanin derivative ( 11 ) proved to be more active and selective than cumanin in the tested breast, cervix, lung, and colon tumor cell lines. This compound was the least toxic against splenocytes (CC 50 = 524.1 µM) and exhibited the greatest selectivity on tumor cell lines. This compound showed a GI 50 of 2.3 µM and a SI of 227.9 on WiDr human colon tumor cell lines. Thus, compound 11 can be considered for further studies and is a candidate for the development of new antitumor agents., Competing Interests: The authors declare no conflict of interest.

In this research, bioactivities toward the Chagas' disease vector Triatoma infestans (Klug) (Hemiptera: Reduviidae) by the essential oil (EO) of Eupatorium buniifolium H. et A. (Asteraceae) are reported. The tests were designed in order to determine ovicidal activity as well as the response to vapor exposure (fumigant) and to topical application (contact toxicity) and as repellent. In the last three bioassays, nymphs from the 3rd and 4th instar were used. The assayed materials were obtained from aerial parts of plants collected during the months of March and December, throughout 4 years, in two locations. The EO samples were subjected to a qualitative analysis by GC-MS and the relative area of each component was reported by GC-FID. The main monoterpene detected was α-pinene and by using a chiral column through GC-MS experiments and having both stereoisomers as standards, we were able to determine that the enantiomer present was S,S-(-)-α-pinene. Although usually in studies of EOs changes in chemical composition are often observed due to the time of collection and the environment where the plant develops, in our case the differences were, with some exception, only at the level of the minor components. The best results were obtained in the experiments to determine ovicidal activity, fumigant action, and repellency. No worthy response was found as insecticide in the trials designed for contact toxicity. The results of the studied bioactivities were independent of the location, month, and year of collection of the plant material. This behavior provides an interesting scope in relation to the potential use of this natural blend for the control of this insect at the nymph stage as repellent as well as for decreasing the population by ovicidal effect. Notably, in the course of the two-choice repellency test, it was possible to demonstrate recognition of one of the enantiomers of the α-pinene, giving rise to a non-common chirality/response effect. In this assay, the levorotatory isomer was the most active as repellent. Considering the abundance of the wild plant under study and the fact that its EO is easy to obtain, it is suggested that it could be an adequate natural resource to control this vector in a sustainable way as a complementary approach to conventional methods.

Several natural and synthetic coumarins were assayed against different cancer cell lines. Four of them have shown cytotoxicity against a panel of three human solid tumor cell lines (HeLa, T-47D, and WiDr) and a clearly activity/hydrophobicity relationship. Compound 13 proved to be the most active product in all cell lines tested, with values of 8.0 (±0.38) μM against HeLa cells and also able to inhibit Taq DNA polymerase. This dual activity of 13 makes it a candidate to be considered as a "lead" compound in the search for novel antitumor drugs.

Enantiomerically pure anti-β-amino alcohols were synthesized from optically pure α-(N,N-dibenzylamino)benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at -78 °C and subsequent in situ addition of Grignard reagents. Besides anti-β-amino alcohols, anti-2-amino-1,3-diols and anti-3-amino-1,4-diols were obtained in good yields (60-95%) and excellent stereoselectivity (de > 95%). Our technique is compatible with free hydroxyl groups present in the substrate. To demonstrate the versatility of the method, spisulosine and sphinganine were synthesized in two steps from the appropriate N,N-dibenzyl-l-aminobenzyl ester in 42% and 45% yield, respectively.

Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-Benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (±0.38) μM against HBL-100 cells., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

In this study, we synthesized a series of phenylpropanoic acid derivatives based on modifications at four selected points of the molecular scaffold. The in vitro antiproliferative activities of the compounds were examined in representative human solid tumor cell lines. A SAR was established pointing out the relevance of the substituents. The best activity profiles were obtained for the derivatives bearing more lipophilic esters (GI50 3.1-21 microM).

A series of analogs were synthesized in a straightforward manner from naturally available sesquiterpenes ilicic acid and tessaric acid. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D and WiDr. The most potent analog induced considerably growth inhibition in the range 1.9-4.5 microM. Cell cycle studies for tessaric acid derivatives indicated a prominent arrest of the cell cycle at the G(2)/M phase. Damage to the cells was permanent as determine by the so called 24+24 drug schedule.

Samarium(II) iodide promotes the stereoselective synthesis of cis-beta-alkoxy-gamma-alkyl-gamma-lactones under mild conditions starting from linear precursors. The in vitro antiproliferative activities were examined in the human solid tumor cell lines from diverse origin A2780, SW1573, and WiDr. From the growth inhibition data a structure-activity relationship was obtained. Overall the results point to the relevant role of cis-beta-alkoxy-gamma-alkyl-gamma-lactones as novel scaffolds for the development of new anticancer drugs.

In this study, we synthesized a series of enantiomerically pure (2R,3S)-disubstituted tetrahydropyranes with diverse functional groups using known methodologies. In addition to the tert-butyl dimethyl silyl group, other common protecting groups for hydroxyl groups such as allyl, acetate, and benzoate were used to obtain appropriate derivatives. Pure compounds were evaluated in vitro against HL60 human leukemia cells and MCF7 human breast cancer cells. From the growth inhibition data a structure-activity relationship was obtained. Overall the results point to the relevant role of the tert-butyl dimethyl silyl group in the modulation of cytotoxic activity.

A series of sesquiterpene compounds possessing both eudesmane and eremophilane skeletons were tested as gastric cytoprotective agents on male Wistar rats. The presence of an alpha,beta-unsaturated aldehyde on the C-7 side chain together with a hydroxyl group at C-4 is the requirement for the observed antiulcerogenic activity. In an attempt to establish new molecular structural requirements for this gastric cytoprotective activity, a structure-activity study was performed.

Allelochemical effects were observed when Tribolium castaneum (Herbst) adults were treated with Baccharis salicifolia (Ruiz & Pavon) Pers essential oil. The main biological activities were toxicity and repellence. Terpenes present in the essential oil were identified by GC-MS, and some authentic samples were tested to assess their activity individually. The most acutely toxic compounds after 3 days were beta-pinene and pulegone. Most of the monoterpenes elicited symptoms indicative of neurotoxicity. The most repellent compound was alpha-terpineol. Toxic and repellent effects of chemical derivatives of the major sesquiterpene present in B salicifolia essential oil, as well as a series of monoterpenes, were evaluated in order to investigate structure-activity relationships. The reduced derivatives of the monoterpenes and sesquiterpenes were more repellent that their carbonyl analogues. In addition, unsaturation in the germacrane skeleton enhanced repellent activity.

Eight eudesmane and eremophilane sesquiterpenes administered to Tribolium castaneum larvae caused different allelochemical effects. Topical application of 3-oxo-gamma-costic acid produced the greatest lengthening in the duration of the pupal stage. Morphological deformities were found, specifically when ilicic, costic, and gamma-costic acids and costic aldehyde were used. Ilicic acid exhibited the major toxicity 72 hr following topical application. All compounds were significantly toxic at the end point of the experiment (60 days). Treated surface toxicity was lower than when topical assays were carried out. Responses to tessaric acid in choice bioassays had the highest attractive effect. Maximum repellency was caused by the 3-oxo-gamma-costic acid. However, experimental series carried out using gamma-costic acid, eremophilan-1(10),2,11(13)-trien-12-oic acid, costic aldehyde, and ilicic aldehyde showed no clear response.