Numerous numbers of biologically active agents have been identified for their diverse therapeutic functions. Detailed investigations of phytochemicals for antiviral activities have assumed greater importance in the last few decades. A wide variety of active phytochemicals, including the flavonoids, terpenoids, organosulfur compounds, limonoids, lignans, sulphides, polyphenolics, coumarins, saponins, chlorophyllins, furyl compounds, alkaloids, polyines, thiophenes, proteins and peptides have been found to have therapeutic applications against different genetically and functionally diverse viruses. The antiviral mechanism of these agents may be explained on basis of their antioxidant activities, scavenging capacities, inhibiting DNA, RNA synthesis, inhibition of the viral entry, or inhibiting the viral reproduction etc. Large number candidate substances such as phytochemicals and their synthetic derivatives have been identified by a combination of in vitro and in vivo studies in different biological assays. In this article we have made attempts to extensively review and provide comprehensive description of different phyto-antiviral agents. We have examined the recent developments in the field of plant derived antiviral agents. The major advances in the field of viral interactions in various biological assays have been summarized. In addition sources of origin, major viral studies mechanistic action and phase trials of various phytoantiviral agents have been included in the review.

Cancer chemoprevention refers to the use of pharmacological agents to inhibit, delay or reverse the multi-step process of carcinogenesis. The last two decades in particular have witnessed explosive growth in this emerging field of cancer chemoprevention. Extensive efforts to evaluate possible application of various chemopreventive agents, in individuals at high risk of neoplastic development have been carried out. Epidemiological studies suggest a protective role of several agents in reducing the risk of cancer. The protective action of all these agents is explained as a combination of various proposed mechanisms involving anti-oxidant, anti-inflammatory, immunomodulatory action, apoptosis induction, molecular association with carcinogen, cell cycle arrest, cell differentiation induction, antimicrobial effect, and anti- angiogenesis etc. Large numbers of candidate substances such as phytochemicals and their synthetic derivatives have been identified by a combination of in vitro and in vivo studies in a wide range of biological assays. However, a comprehensive description of these chemopreventive agents has not been extensively reviewed. In this review we discuss cancer chemopreventive agents in relation to their source, efficacy in cancer chemopreventive action in vivo and epidemiological data. The experimental carcinogenesis studies in different biological models, in addition to the contribution from our laboratory are summarized.

Currently, breast cancer is considered as one of the leading causes for death in women in the United States. Consumption of natural products has received considerable attention in recent years as a possible approach for cancer prevention in general population. There are numerous cancer preventive agents present in the natural products, which may contribute to their chemopreventive properties. During the past two decades, numerous chemopreventive agents have been isolated and/or synthesized and evaluated for their efficacy in a variety of biological assays. To this end, we have established and utilized mouse mammary gland organ culture model (MMOC) as a bioassay for identifying chemopreventive agents. Mammary glands respond to growth promoting hormones and the physiological differentiation can be reproduced in MMOC in chemically defined medium by altering hormonal milieu. Both estrogen and progesterone dependent (mammary ductal lesions, MDL) and independent (mammary alveolar lesions, MAL) precancerous lesions can be induced in response to a 24 hour exposure to DMBA in MMOC. Suppression of the incidence and multiplicity of these lesions by a possible chemopreventive agent can serve as a tool to evaluate efficacy of potential experimental agents. Using this approach, we have evaluated more than 200 synthetic and natural product-derived chemopreventive agents in this model as a part of the National Cancer Institute-supported projects. Many of these chemopreventive agents expressing significant activity have progressed to the in vivo experimental mammary carcinogenesis studies. Thus, this bioassay has proven to be a valuable tool for screening cancer chemopreventive agents for breast cancer prevention and for understanding molecular mechanism(s) of action of these agents. In this comprehensive review, we provide a complete list of chemopreventive agents evaluated for the efficacy against development of mammary alveolar lesions (MAL) in MMOC along with the recent developments in this area. The structure-activity relationships for many chemopreventive agents evaluated in the MMOC model have been discussed.

The conversion of 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-AIR (CAIR) represents an unusual divergence in purine biosynthesis: microbes and nonmetazoan eukaryotes use class I PurEs while animals use class II PurEs. Class I PurEs are therefore a potential antimicrobial target; however, no enzyme activity assay is suitable for high throughput screening (HTS). Here we report a simple chemical quench that fixes the PurE substrate/product ratio for 24h, as assessed by the Bratton-Marshall assay (BMA) for diazotizable amines. The ZnSO4 stopping reagent is proposed to chelate CAIR, enabling delayed analysis of this acid-labile product by BMA or other HTS methods.

Lung cancer is the most common cancer worldwide, accounting for 1.2 million new cases annually. Despite the availability of several novel medications, very few have been found to be widely applicable or effective. Hence, the aim of present study was to assess the efficacy of Zapotin, a phytochemical present in the Mexican fruit Sapote blanco (Casimiroa edulis), in lung epithelial cells. Zapotin was chemically synthesized and the effects were evaluated on several human non-small cell lung cancer cell lines (A549 (p53 wild type), Calu-1(p53 null), H1993 (p53 mutated)) and the Normal Human Bronchial epithelial cell line (BEAS-2b) using cell proliferation assay (MTT Assay & Cell count method), apoptosis assay (TUNEL Assay), western blot analysis and RT-PCR. Significant growth inhibition of 66.91% and apoptosis was found to be induced in the A549 cells when treated with 1 μM zapotin for 72 hrs. On the other hand, no significant growth inhibition was noted for Beas-2b under the same conditions. Furthermore, the western blot analyses indicated that zapotin increased p53 and p21 protein expression in A549 cells but not in Beas-2b cells. Studies for p53 mRNA expression were completed on A549 and Beas-2b subsequent to treatment with zapotin and it showed to have no significant changes. This suggested that the activation of p53 is at protein level instead of transcriptional level. This is the first report to indicate that zapotin acts through p53 mediated pathway in wild-type p53 positive A549 cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5694.