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Flavopiridol, a synthetic flavonoid derived from rohitukine, stands out as a powerful cyclin-dependent kinase (CDK) inhibitor with significant anticancer properties. Its action mechanisms involve inducing cell cycle arrest, triggering apoptosis, and inhibiting transcription across various cancer types. Despite these promising effects, flavopiridol's clinical use has been hampered by issues related to toxicity and drug resistance. This study aims to comprehensively review flavopiridol's mechanisms of action, structure-activity relationships, synthetic derivatives, pharmacokinetics, and its potential role in clinical applications, with a focus on how combination therapies can enhance its efficacy and address resistance challenges in cancer treatment. A thorough analysis of key studies was performed, examining flavopiridol's anticancer properties, emphasizing its structure-activity relationships, synthetic modifications, and clinical outcomes. The anticancer effects of flavopiridol are primarily driven by its inhibition of CDKs, induction of apoptosis, promotion of oxidative stress, and antiangiogenic activity. Modifications in its chemical structure, especially in the D ring, have shown a significant impact on its CDK inhibitory potency. Several synthetic derivatives have also demonstrated enhanced anticancer activity. While preclinical models highlight flavopiridol's potential in treating cancers such as leukemia and solid tumors, clinical trials have brought attention to its limitations, particularly regarding toxicity and resistance. However, flavopiridol remains a promising candidate for cancer therapy, especially when used in combination with other treatments. Future research efforts should focus on refining its therapeutic profile, minimizing toxicity, and investigating synergistic treatment combinations, including those with immunotherapy. Understanding the mechanisms of resistance and discovering predictive biomarkers will be crucial for its effective integration into clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to analyze the combined impact of CO 2 and drought stress at the flowering stage on carbon (C), nitrogen (N), and CN ratios in leaves, stem, and grains of bread wheat. Six diverse bread wheat genotypes, comprised of two commercial checks, two landraces, and two synthetics derivatives, were grown at two levels of CO 2 , i.e., 400 ppm and 800 ppm, and drought stress was imposed at the flowering stage through progressive soil drying. Stem, leaf, and grain samples were taken at maturity and concentrations of C and N were determined. Our results indicate that the threshold value of fraction of transpirable soil water (C FTSW ) at which it diverges towards closure of stomata was different among genotypes and a higher range of values was estimated under elevated CO 2 . Drought significantly increased C levels in leaves and N levels in grains but decreased N levels in leaves, which increased CN ratios in leaves. In contrast, drought significantly reduced CN ratios in grains. Genotypes differed significantly in N content in grains, where the landrace derivative L 2 maintained the highest N content. Moreover, pronounced changes in leaf N and CN ratios were induced by the combination of elevated CO 2 and drought stress. Additionally, combined correlation and biplot analyses indicate a strong positive association of grain CN (GCN) with grain number, weight, and grain yield. These effects possibly interact with drought to strongly interfere with the impact of elevated CO 2 . The differential performance of the tested genotypes shows that selection of appropriate germplasm is essential to maintain agricultural production.

Coronarin E is a main diterpene ever isolated from Hedychium yunnanense . With the aim to enlarge its potential application, four butenolide derivatives (compounds 4a , 4b , 5a and 5b ) were obtained from coronarin E via synthetic method, and their antibacterial effects were also evaluated. It is noteworthy that compounds 5a and 5b exhibited stronger antibacterial activities against most of the tested bacterial strains than ampicillin and kanamycin, two first- and second-line antimicrobials in clinical. For example, minimum inhibitory concentration (MIC) of 5a , 5b , ampicillin and kanamycin against Acinetobacter baumanii were 2, 1, 8 and 4 μg/mL, respectively, and MIC of the four compounds mentioned above against Klebsiella pneumonia were 1, 0.5, 16 and 4 μg/mL, respectively. The current studies not only enrich the structural diversity of diterpenes derived from Hedychium genus, but also provide potent candidates for the development of antibacterial medicines.

Aims: There has been increased scientific interest in bioactive compounds and their synthetic derivatives to promote the development of antimicrobial agents that could be used sustainably and overcome antibiotic resistance., Methods: We conducted this scoping review to collect evidence related to the antimicrobial potential of diverse natural compounds from Zingiberaceae plants and their synthetic derivatives. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews guidelines. The literature search was conducted using PubMed, Web of Science and Scopus electronic databases for relevant studies published from 2012 to 2023. A total of 28 scientific studies fulfilled the inclusion criteria. The authors of these studies implemented in vitro and in silico methods to examine the antimicrobial potency and underlying mechanisms of the investigated compounds., Result: The evidence elucidates the antimicrobial activity of natural secondary metabolites from Zingiberaceae species and their synthetic derivatives against a broad panel of gram-positive and gram-negative bacteria, fungi and viruses., Conclusion: To date, researchers have proposed the application of bioactive compounds derived from Zingiberaceae plants and their synthetic analogues as antimicrobial agents. Nevertheless, more investigations are required to ascertain their efficacy and to broaden their commercial applicability., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Genital herpes, most frequently caused by herpes simplex virus 2 (HSV-2) infection, is one of the most prevalent sexually transmitted infections. The current rationale for the treatment of HSV-2 infection involves nucleoside analogs (e.g. acyclovir) to suppress reactivation. Enzymatic oxysterols are endogenous 27-carbon atoms molecules produced by enzymatic cholesterol oxidation, and recently emerged as a broad-spectrum host targeting antivirals. In this study, we screened selected members of an in-house synthesized library of oxysterol analogs for their activity against HSV-2, identifying three compounds, named PFM064, PFM067, and PFM069, endowed with 50% effective concentrations (EC 50 ) in the micromolar range, without exerting any apparent cytotoxicity. Moreover, the results obtained showed the ability of the novel derivatives to inhibit both cell-to-cell fusion induced by HSV-2, and the production of an intracellular viral progeny. Further experiments performed with PFM067 (which was selected for more-in-depth studies as the most effective synthetic analog) showed that these molecules act in a late stage of HSV-2 replicative cycle, by sequestering viral glycoproteins in the Golgi compartment, and likely inhibiting the nuclear egress of neo-synthetized viral capsids. Taken together, these results point to PFM067 as a promising chemical scaffold for the development of novel herpetic antivirals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Andrea Civra, David Lembo, Giuseppe Poli are the founders of Panoxyvir Ltd., a start-up developing the use of specific oxysterols as broad-spectrum antiviral agents. All other authors: none to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The improvement of cancer chemotherapy remains a major challenge, and thus new drugs are urgently required to develop new treatment regimes. Curcumin, a polyphenolic antioxidant derived from the rhizome of turmeric (Curcuma longa L.), has undergone extensive preclinical investigations and, thereby, displayed remarkable efficacy in vitro and in vivo against cancer and other disorders. However, pharmacological limitations of curcumin stimulated the synthesis of numerous novel curcumin analogs, which need to be evaluated for their therapeutic potential. In the present study, we calculated the binding affinities of 50 curcumin derivatives to known cancer-related target proteins of curcumin, i.e., epidermal growth factor receptor (EGFR) and nuclear factor κB (NF-κB) by using a molecular docking approach. The binding energies for EGFR were in a range of −12.12 (±0.21) to −7.34 (±0.07) kcal/mol and those for NF-κB ranged from −12.97 (±0.47) to −6.24 (±0.06) kcal/mol, indicating similar binding affinities of the curcumin compounds for both target proteins. The predicted receptor-ligand binding constants for EGFR and curcumin derivatives were in a range of 0.00013 (±0.00006) to 3.45 (±0.10) µM and for NF-κB in a range of 0.0004 (±0.0003) to 10.05 (±4.03) µM, indicating that the receptor-ligand binding was more stable for EGFR than for NF-κB. Twenty out of 50 curcumin compounds showed binding energies to NF-κB smaller than −10 kcal/mol, while curcumin as a lead compound revealed free binding energies of >−10 kcal/mol. Comparable data were obtained for EGFR: 15 out of 50 curcumin compounds were bound to EGFR with free binding energies of <−10 kcal/mol, while the binding affinity of curcumin itself was >−10 kcal/mol. This indicates that the derivatization of curcumin may indeed be a promising strategy to improve targe specificity and to obtain more effective anticancer drug candidates. The in silico results have been exemplarily validated using microscale thermophoresis. The bioactivity has been further investigated by using resazurin cell viability assay, lactate dehydrogenase assay, flow cytometric measurement of reactive oxygen species, and annexin V/propidium iodide assay. In conclusion, molecular docking represents a valuable approach to facilitate and speed up the identification of novel targeted curcumin-based drugs to treat cancer.

The use of sunscreens is an established and recommended practice to protect skin from solar-induced damage. Around 30 UV filters can be used in sunscreen products in the European Union, which ought to follow the requirements of the regulation 1223/2009 to ensure their efficacy and safety for humans. Nevertheless, low photostability and putative toxicity for humans and environment have been reported for some UV filters. Particularly, the negative impact in marine organisms has recently raised concern on the scientific community. Therefore, it is important to develop new UV filters with improved safety profile and photostability. Over the last two decades, nearly 200 new compounds have revealed promising photoprotection properties. The explored compounds were obtained through different approaches, including exploration of natural sources, synthetic pathways, and nanotechnology. Almost 50 natural products and around 140 synthetic derivatives, such as benzimidazoles, benzotriazoles, hydroxycinnamic acids, xanthones, triazines, among others, have been studied aiming the discovery of novel, effective, and safer future photoprotective agents. Herein, we provide the reader with an overview about UV filters' challenges and prospects, offering a forward-looking to the next-generation of UV filters.

In this review, we emphasize on evolving therapeutic strategies and advances in the treatment of breast cancer (BC). This includes small-molecule inhibitors under preclinical and clinical investigation, phytoconstituents with antiproliferative potential, targeted therapies as antibodies and antibody-drug conjugates (ADCs), vaccines as immunotherapeutic agents and peptides as a novel approach inhibiting the interaction of oncogenic proteins. We provide an update of molecules under different phases of clinical investigation which aid in the identification of loopholes or shortcomings that can be overcomed with future breast cancer research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity., (© 2021. The Author(s).)

Melanosis is an unsolved problem of the crustacean industry and the cause of great loss of value. This study investigates the effect of two potent, natural antioxidants isolated from olive waste (hydroxytyrosol, HT and 3,4-dihydroxyphenylglycol, DHPG) and three novel HT-derivatives containing selenium and sulfur (dihydroxytyrosyl diselenide, N -hydroxytyrosyl selenourea, and N -hydroxytyrosyl thiourea) on the prevention of melanosis in Atlantic ditch shrimp ( Palaemonetes varians ) during refrigerated storage. These results clearly demonstrate the positive inhibitory effect of DHPG and dihydroxytyrosyl diselenide on delaying melanosis in vivo, although this effect was not dose dependent. The effect was associated with a concomitant-inhibitory effect on tyrosinase activity in vitro. To our knowledge, so far no studies on the prevention of melanosis have been conducted on this small specie of shrimp which is available in large quantities at any time of the year at low cost. Studies with these promising compounds could then be extended to other more economically important species with a greater guarantee of success.

Background: Neglected tropical diseases are a group of infections caused by microorganisms and viruses that affect mainly poor regions of the world. In addition, most available drugs are associated with long periods of treatment and high toxicity which limits the application and patient compliance. Investment in research and development is not seen as an attractive deal by the pharmaceutical industry since the final product must ideally be cheap, not returning the amount invested. Natural products have always been an important source for bioactive compounds and are advantageous over synthetic compounds when considering the unique structural variety and biological activities. On the other hand, isolation difficulties and low yields, environmental impact and high cost usually limit their application as drug per se., Objective: In this review, the use of natural products as prototypes for the semi-synthesis or total synthesis, as well as natural products as promising hits is covered, specifically regarding compounds with activities against trypanosomatids such as Trypanosoma spp. and Leishmania spp., Methods: Selected reports from literature with this approach were retrieved., Conclusion: As summary, it can be concluded that natural products are an underestimated source for designing novel agents against these parasites., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Arnica montana, containing helenalin as its principal active constituent, is the most widely used plant to treat various ailments. Recent studies indicate that Arnica and helenalin provide significant health benefits, including anti-inflammatory, neuroprotective, antioxidant, cholesterol-lowering, immunomodulatory, and most important, anti-cancer properties., Objective: The objective of the present study is to overview the recent patents of Arnica and its principal constituent helenalin, including new methods of isolation, and their use in the prevention of cancer and other ailments., Methods: Current prose and patents emphasizing the anti-cancer potential of helenalin and Arnica, incorporated as anti-inflammary agents in anti-cancer preparations, have been identified and reviewed with particular emphasis on their scientific impact and novelty., Results: Helenalin has shown its anti-cancer potential to treat multiple types of tumors, both in vitro and in vivo. It has also portrayed synergistic effects when given in combination with other anti- cancer drugs or natural compounds. New purification/isolation techniques are also developing with novel helenalin formulations and its synthetic derivatives have been developed to increase its solubility and bioavailability., Conclusion: The promising anti-cancer potential of helenalin in various preclinical studies may open new avenues for therapeutic interventions in different tumors. Thus clinical trials validating its tumor suppressing and chemopreventive activities, particularly in conjunction with standard therapies, are immediately required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The α-glucosidase (EC 3.2.1.20), a calcium-containing intestinal enzyme which is positioned in the cells which cover the intestinal microvilli brush border. The carbohydrates require metabolism by α-glucosidase before being absorbed into the small intestine, and as a result, this enzyme represents a significant drug target for the effective management of diabetes. There are few α- glucosidase inhibitors in the clinical practice that is challenged by several limitations. Thus, new effective and safe therapeutic agents in this class are required. In this regard, plant secondary metabolites are a very promising source to be investigated. Herein in this review, we have focused on the preclinical studies on various glycosides with in vitro α-glucosidase inhibitory activity., Methods: The literature available on various websites such as GoogleScholar, PubMed, Scopus. All the peer-reviewed articles were included without considering the impact factor., Results: The surveyed literature revealed marked inhibitory profile of various glycosides derived from plants, and some of them were extremely potent relatively to the standard, acarbose in preclinical trials and exhibited multiple targeted effects., Conclusion: Keeping in view the results, these glycosides are strong candidates for further, more detailed studies to ascertain their clinical potential and for effective contribution in effective management of diabetes, where multiple targets are required to address., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Natural products with diverse bioactivities and structures are an important source of novel chemicals with pharmaceutical potentials. Combinations of bioactive compounds with classical antimicrobial agents against drug-resistant or low-susceptible Candida spp. have been studied. Guttiferone-A and its derivatives were combined with fluconazole through the checkerboard method and tested against Candida spp. The results obtained, especially the Fractional Inhibitory Concentration Index (FICI) determined to the combinations, suggests promising results on the treatment of Candida infections, principally for species that present resistance or low antifungal susceptibility. The best result was seen for C. krusei, in which a synergic action of the association between fluconazole and Guttiferone-A resulted in a reduction of more than 100-fold in the alone inhibitory concentration (MIC) of fluconazole. Synergism was also noted in the association of fluconazole with the synthetic derivatives LFQM-79, LFQM-80 and LFQM-81 against C. glabrata, with reduction of up to four times in the alone IC of fluconazole. These results suggest the possibility of combined administration with reduction of doses and side effects of drugs conventionally used against Candida spp. and the promising therapeutic action of Guttiferone-A., (Copyright © 2018. Published by Elsevier Masson SAS.)

Piplartine ( 1 ) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound ( E )-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate ( 10 ), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.

Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared to other derivatives, with minimum inhibitory concentration (MIC) at 25 μM. Moreover, 9 was active against several T. vaginalis fresh clinical isolates. Hemolysis assay demonstrated that 9 presented a low hemolytic effect. Importantly, 25 μM 9 was not cytotoxic against the Vero cell lineage. Finally, we demonstrated that compound 9 acts synergistically with metronidazole against a T. vaginalis metronidazole-resistant isolate. This report reveals the high potential of the triterpenoid derivative 9 as trichomonicidal agent.

Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine Cortex Fraxini . The twig skin or trunk bark of Cortex Fraxini are used by herb doctors as a mild, bitter liver and gallbladder meridians' nontoxic drug as well as dietary supplement. Recently, with a variety of novel esculetin derivatives being reported, the molecular mechanism research as well as clinical application of Cortex Fraxini and esculetin are becoming more attractive. This mini-review will consolidate what is known about the biological activities, the mechanism of esculetin and its synthetic derivatives over the past decade in addition to providing a brief synopsis of the properties of esculetin.

Chagas disease, caused by Trypanosoma cruzi, affects six to seven million people worldwide. Treatment is based on benznidazole, producing several side effects and debatable efficacy, highlighting the need for new alternative drugs. We investigated the activity of four C-4 functionalized azlactone derivatives (EPA-27, EPA-35, EPA-63 and EPA-91) as potential T. cruzi inhibitors. Screening with epimastigotes indicated EPA-35 as the best compound (IC50/24 h: 33 μM). This compound was 14.1 times more potent against intracellular amastigotes (IC50/24 h: 2.34 μM). Treatment of infected Vero cells for 72 h (up to 30 μM EPA-35) resulted in a dose-dependent decrease in number of trypomastigotes and amastigotes released in the supernatant, but the amastigote/trypomastigote ratio remained constant, indicating that amastigote growth was disturbed, but cell differentiation was unaffected. Analysis of treated epimastigotes by flow cytometry indicated that the plasma membrane remained intact, but there was a significant decrease in mitochondrial membrane potential. The pattern of cell distribution in the cell cycle stages (G1, G2, M) was unaltered in treated epimastigotes, indicating a trypanocidal rather than a trypanostatic activity. Scanning electron microscopy and flow cytometry showed epimastigotes with a round shape and decrease in cell size. Taken together, our data indicate that the EPA-35 is effective against T. cruzi. Synthetic transformation of EPA-35 into other derivatives may provide promising compounds for further evaluation against this parasite., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

2-Methoxyestradiol (2ME2), an estrogen hormone metabolite is a potential cancer chemotherapeutic agent. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. This anticancer drug candidate has been explored extensively in last twenty years for its detailed chemistry and pharmacology. Present review is an update of its chemistry and biological activity. It also extends an assessment of potential of 2ME2 and its analogues as possible anticancer drug in future., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action., Method: Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM)., Results: Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53(+/+) colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells., Conclusion: The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity., (Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Caffeic acid and its naturally occurring derivative caffeic acid phenethyl ester (CAPE) have antiproliferative and cytotoxic properties in a variety of cancer cell lines without displaying significant toxicity toward healthy cells, and are considered to be potential anticancer agents. However, little is known about their effects on prostate cancer cells. We synthesized and evaluated the effects of caffeic acid, CAPE (2) and 18 synthetic derivatives on cell viability and androgen-dependent cell proliferation, subcellular localisation and expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) in LNCaP human hormone-dependent prostate cancer cells. Several synthetic derivatives of CAPE were strong, concentration-dependent cytotoxic agents in LNCaP cells with IC50 values in the 6.8-26.6 μM range, potencies that were up to five-fold greater than that of CAPE (33.7±4.0 μM). A number of caffeic acid derivatives were inhibitors of androgen-stimulated LNCaP cell proliferation with concomitant inhibition of DHT-stimulated PSA secretion. Compound 24 was the most cytotoxic and antiproliferative caffeic acid derivative (IC50 values of 6.8±0.3 and 2.4±0.8 μM, respectively) inhibiting DHT-stimulated cell proliferation and PSA secretion statistically significantly at concentrations as low as 0.3 μM. Exposure to DHT increased cytoplasmic and nuclear AR levels and co-treatment with increasing concentrations of compound 24 or CAPE (2), notably, further increased these levels. In conclusion, a number of synthetic derivatives of caffeic acid are potent inhibitors of androgen-dependent prostate cancer cell proliferation and viability, acting, at least in part, via an antiandrogenic mechanism that involves increased nuclear accumulation of (presumably inactive) AR., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ribosomally synthesized natural antimicrobial peptides (AP) and their synthetic derivatives are small, cationic, amphipathic molecules of 12-50 amino acids with unusually broad activity spectra. These peptides kill microorganisms by a common mechanism, which involves binding to the lipid bilayer of biological membranes, forming pores, and ultimately followed by cell lysis. Several AP from mammals, amphibians, insects, plants and their synthetic derivatives demonstrate promising in vitro activity against various pathogenic fungi including azole-resistant Candida albicans strains. In addition to their antimicrobial activity, some AP such as lactoferrin, interact with a variety of host cells and can increase the activity of natural killer and lymphokine activated killer cells. Pretreatment of polymorphonuclear neutrophil leukocytes (PMN) or monocytes with these AP also may upregulate superoxide release. AP as potential new antifungal agents offer some advantages, such as rapid killing of pathogenic fungi and the difficulty to raise mutants resistant to these peptides. AP are limited by their nonselective toxicity, stability, immunogenicity and their costs of production. Potential clinical applications of AP in the future have to be further explored in preclinical and clinical studies to assess their impact as a new class of antifungals., (1999 Blackwell Science Ltd.)