€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DISS ABSTR INT [B]***** Lu H Part I. The synthesis and structure-activity relationship study of azo dye related HIV replication inhibitors. Part II. Plant isolation of signalling pathways inhibitors as anticancer agents. In: Diss Abstr Int [B] (1995) 55(12):5348 ISSN: 0419-4217 Since HIV-1 was identified as the causative agent of AIDS, many polyanionic compounds have been found possessing anti-HIV activity. Among them, several commercial dyes, such as Chicago Sky Blue, Even's Blue, Congo Red, and Direct Orange 15, attracted a lot of attention, because of their specificity and different mechanisms of actions from AZT. Quinobene, which was modeled after Chicago Sky Blue, surpassed this dye in activity. But two drawbacks prevented quinobene from further consideration in clinical evaluation: low bioavailability and highly intense color. In this part of my research, a series of compounds, structurally related to quinobene and Direct Orange 15, were prepared in an effort to improve these pharmacological properties, and to provide a structure-activity relationship (SAR). Several compounds of much lighter color showed potent activity in the NCl in vitro assay. Some interesting SARs have been observed, such as the observation that azo linkages could be replaced with other groups of similar size and configuration, such as amide, without loss of activity. Intracellular signal transduction pathways play an important role in tumorigenesis, because two thirds of known proto- oncogenes act by coding for components of these pathways. Proteins encoded by these oncogenes, which are constitutively active analogs, under certain circumstances, lead to the cell's neoplastic transformation. Therefore, oncogene signal transduction is a logical target at which to direct a new anticancer drug development. In this research, specific components targeted included various growth factors (vasopressin, bradykinin, and platelet-derived growth factor), and enzymes (phosphoinositide specific phospholipase C, phosphatidylinositol-3-kinase, tyrosine protein kinase, and protein kinase C). A large number of plant extracts were assayed against these targets. Four plant extracts, Geranium carolinium, Polygonum pennsylvanicum, Daucus carota, and Rhododendron catawbinse, were found active. Bioassay-directed fractionation of these active extracts led to potent inhibitors. A pure compound from R. catawbinse, dendropanoxide, was identified for the first time as a PKC inhibitor. A herbicide, oryzalin, was accidentally found to be an excellent inhibitor against Ca++ signalling and several tumor cell lines. Several other active compounds were also isolated, but were not identified due to insufficient quantities. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AADAA-I9511595) Registry Numbers EC 2.7.1.- (Protein Kinase C) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Lu H Part I. The synthesis and structure-activity relationship study of azo dye related HIV replication inhibitors. Part II. Plant isolation of signalling pathways inhibitors as anticancer agents. In: Diss Abstr Int [B] (1995) 55(12):5348 ISSN: 0419-4217 Since HIV-1 was identified as the causative agent of AIDS, many polyanionic compounds have been found possessing anti-HIV activity. Among them, several commercial dyes, such as Chicago Sky Blue, Even's Blue, Congo Red, and Direct Orange 15, attracted a lot of attention, because of their specificity and different mechanisms of actions from AZT. Quinobene, which was modeled after Chicago Sky Blue, surpassed this dye in activity. But two drawbacks prevented quinobene from further consideration in clinical evaluation: low bioavailability and highly intense color. In this part of my research, a series of compounds, structurally related to quinobene and Direct Orange 15, were prepared in an effort to improve these pharmacological properties, and to provide a structure-activity relationship (SAR). Several compounds of much lighter color showed potent activity in the NCl in vitro assay. Some interesting SARs have been observed, such as the observation that azo linkages could be replaced with other groups of similar size and configuration, such as amide, without loss of activity. Intracellular signal transduction pathways play an important role in tumorigenesis, because two thirds of known proto- oncogenes act by coding for components of these pathways. Proteins encoded by these oncogenes, which are constitutively active analogs, under certain circumstances, lead to the cell's neoplastic transformation. Therefore, oncogene signal transduction is a logical target at which to direct a new anticancer drug development. In this research, specific components targeted included various growth factors (vasopressin, bradykinin, and platelet-derived growth factor), and enzymes (phosphoinositide specific phospholipase C, phosphatidylinositol-3-kinase, tyrosine protein kinase, and protein kinase C). A large number of plant extracts were assayed against these targets. Four plant extracts, Geranium carolinium, Polygonum pennsylvanicum, Daucus carota, and Rhododendron catawbinse, were found active. Bioassay-directed fractionation of these active extracts led to potent inhibitors. A pure compound from R. catawbinse, dendropanoxide, was identified for the first time as a PKC inhibitor. A herbicide, oryzalin, was accidentally found to be an excellent inhibitor against Ca++ signalling and several tumor cell lines. Several other active compounds were also isolated, but were not identified due to insufficient quantities. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AADAA-I9511595) Registry Numbers: EC 2.7.1.- (Protein Kinase C) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DIABETES RESEARCH***** Swanston-Flatt SK Day C Flatt PR Gould BJ Bailey CJ Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. In: Diabetes Res (1989 Feb) 10(2):69-73 ISSN: 0265-5985 Twelve plants used for the traditional treatment of diabetes mellitus in northern Europe were studied using normal and streptozotocin diabetic mice to evaluate effects on glucose homeostasis. The plants were administered in the diet (6.25% by weight) and/or as decoctions or infusions in place of drinking water, to coincide with the traditional method of preparation. Treatment for 28 days with preparations of burdock (Arctium lappa), cashew (Anacardium occidentale), dandelion (Taraxacum officinale), elder (Sambucus nigra), fenugreek (Trigonella foenum-graecum), guayusa (Ilex guayusa), hop (Humulus lupulus), nettle (Urtica dioica), cultivated mushroom (Agaricus bisporus), periwinkle (Catharanthus roseus), sage (Salvia officinale), and wild carrot (Daucus carrota) did not affect the parameters of glucose homeostasis examined in normal mice (basal plasma glucose and insulin, glucose tolerance, insulin-induced hypoglycaemia and glycated haemoglobin). After administration of streptozotocin (200 mg/kg) burdock and nettle aggravated the diabetic condition, while cashew, dandelion, elder, fenugreek, hop, periwinkle, sage and wild carrot did not significantly affect the parameters of glucose homeostasis studied (basal glucose and insulin, insulin-induced hypoglycaemia, glycated haemoglobin and pancreatic insulin concentration). Guayusa and mushroom retarded the development of hyperglycaemia in streptozotocin diabetes and reduced the hyperphagia, polydipsia, body weight loss, and glycated haemoglobin. Mushroom also countered the initial reduction in plasma insulin and the reduction in pancreatic insulin concentration, and improved the hypoglycaemic effect of exogenous insulin. These studies suggest the presence of potentially useful antidiabetic agents in guayusa and mushroom. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****REVISTA DE GASTROENTEROLOGIA DEL PERU***** Guevara JM Chumpitaz J Valencia E [The in vitro action of plants on Vibrio cholerae] Accion in vitro de plantas sobre Vibrio cholerae. In: Rev Gastroenterol Peru (1994 Jan-Apr) 14(1):27-31 ISSN: 1022-5129 (Published in Spanish) Natural products of several plants, according to the geographic location, are used by Peruvian people in the popular treatment of diarrhea, with good success. When cholerae cases appeared in Peru, we were interested to know the "in vitro" effect against Vibrio cholerae 01, of these useful plants to treat diarrhea. The following plants were tested: Cichorium intybus, Althaea officinalis, Psorela glandulosa, Geranium maculatum, Punica granatum, Malus sativa, Cydonia oblonga, Chenopodium ambrosoides, Krameria triandria, Tea chinensis, Daucus carota, Persea gratissima, Psidium guayaba and Lippia dulcis. Decoction or infusion of the plants were used in the "in vitro" experiments. The following plants showed no "in vitro" effect against V. cholerae: Cichorium intybus, Althaea officinalis, Psorela glandulosa, Geranium maculatum, Chenopodium ambrosoides, Krameria triandria, Psidium guayaba, Lippia dulcis and Daucus carota. Decoction of Malus sativa and Cydenia oblonga showed bactericidal effect for their acidity and stone avocado (Persea gratissima) a late bactericidal effect. Tea infusion and the decoction of Punica granatum peel, showed the best bactericidal effect and we suggest to use them as to stop cholera spreading. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€