Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.

Biosyntheses of geranic acid and citronellic acid from monoterpene alcohols by Saccharomyces cerevisiae

ABSTRACT Geraniol is one of the important aromatic ingredients in alcoholic beverages. Bioconversions of geraniol to other terpenoids and genes involved in the oxidation of geraniol were investigated. Geranic acid and citronellic acid were detected in yeast culture, where geraniol or nerol was added. Addition of citral, a mixture of geranial and neral, resulted in the production of geranic acid and citronellic acid, whereas the addition of citral or citronellal resulted in the production of citronellic acid, suggesting that citronellic acid might be produced through the conversion of citral to citronellal followed by the oxidation of citronellal. Consumption of geraniol and production of geranic acid, citronellic acid, and citronellol were affected in adh1Δ, adh3Δ, adh4Δ, and sfa1Δ yeast strains, which possess single deletion of a gene encoding alcohol dehydrogenase. This is the first report of the bioconversion of monoterpene alcohols, geraniol and nerol, to geranic acid and citronellic acid in yeast culture.

Behavioral Responses of the Common Bed Bug to Essential Oil Constituents

Botanical-derived pesticides have arisen as an attractive alternative to synthetic insecticides to effectively manage infestations of bed bugs (Cimex lectularius L.). While information on contact, residual, and fumigant toxicity of plant-essential oils against bed bugs have been recently published, there is a gap of information regarding the repellent activity of these products and their constituents. Identification of essential oil constituents (EOCs) with repellent activity will help develop potentially efficacious essential oil-based formulations for use in bed bug management programs. In this study, we first screened fresh and 24 h-aged residues of geraniol, eugenol, carvacrol, thymol, citronellic acid, linalool, menthone, trans-cinnamaldehyde, α-pinene, β-pinene, and limonene for avoidance behavior from individual bed bugs with a video-tracking system. Six EOCs, geraniol, eugenol, citronellic acid, thymol, carvacrol, and linalool were further evaluated overnight in choice tests to determine whether 24-h aged residues were still avoided by groups of bed bugs. While bed bugs avoided resting on filter papers treated with 24-h aged residues of geraniol, eugenol, citronellic acid, and carvacrol, bed bugs aggregated in areas treated with linalool-aged residues. Barriers of EOCs did not prevent bed bugs from reaching a warmed blood source and acquiring blood meals. Our results show that novel formulations of natural product insecticides that include geraniol, eugenol, carvacrol, or citronellic acid have potential to repel bed bugs. The presence of host-associated cues might interfere with these responses.

Evaluation of antioxidant and antimicrobial activity of Ziziphora ‎clinopodiodes essential oil eluted at different times

Objective: Ziziphora clinopodioides is an edible medicinal plant belongs to the Labiatae family that widespread all over Iran. It used as culinary and also in cold and cough treatments in Iran. The aim of present work was to evaluate the effect of different timeframes during the hydrodistillation on essential oil composition, antimicrobial and antioxidant activity. Materials and Methods: The essential oil of Z. clinopodiodes was extracted via hydrodistillation with Clevenger apparatus. The fractions of essential oil were captured at 6 times from the beginning of the distillation: (10, 20, 60, 120, 180 and 240 min). The fractions of essential oil were analyzed by GC/MS and their antibacterial, antifungal and antioxidant activities were studied by Disk - well diffusion and DPPH methods respectively. Results: Six distillation times and whole essential oil were captured during the hydrodistillation. Essential oil yield dropped off significantly during distillation progressed (1.0% for 10 min and 0.025 for 240 min). 1,8 Cineol, Isomenthone, Pulegone, Piperitenone and Citronellic acid were major compounds in fractions and they were affected by distillation times. Pulegone was major compound in all of essential oils. In antioxidant activity assay, whole essential oil was stronger than was stronger than positive control and fractions of essential oil, because of higher levels of Isomenthone, Piperitenone and Citronellic acid. Strongest antimicrobial activity against S. aureus, E. coli and C. albicans was observed from 10 min fraction. Conclusion: Our results indicated that distillation time can create essential oils with specific properties and we can achieve to more efficient essential oil in short times.