Evaluation of safety margins of Chenopodium album seed decoction: 14-day subacute toxicity and microbicidal activity studies

<p>Abstract</p> <p>Background</p> <p>Sperm immobilizing activity and plausible mechanism of action of <it>Chenopodium album </it>seed decoction (CAD) have been elucidated in our earlier studies. The present study has been carried out to explore the safety standards of CAD along with microbicidal properties as prerequisite for its use as a topically applicable vaginal contraceptive.</p> <p>Methods</p> <p>The safety standards of CAD were assessed by a) Hemolytic index determination using rabbit erythrocytes, to set the doses of the other experiments, b) Dermal irritancy test using refined version of Draize scoring system on rabbits, c) Possible effect on local tissues and reproductive performance in female rats after fourteen daily single dose application, d) PCNA staining- to evaluate the effect of CAD on vaginal tissue proliferation, e) TUNEL assay- to examine its ability to induce <it>in situ </it>apoptosis in the vaginal tissue sections of the treated animals, and f) Microbicidal activity- to explore the effect of CAD on the growth of <it>Lactobacillus acidophilus </it>and <it>Candida albicans</it>.</p> <p>Results</p> <p><it>In vitro </it>irritation studies on rabbit erythrocytes revealed the hemolytic index of CAD to be 8.2 mg/ml. The dermal irritation test showed it to be a non-irritant even at higher doses. Intra vaginal application of CAD in rat vagina for 14 consecutive days caused slight reversible inflammation on vaginal epithelial cells at doses as high as 82 mg/ml. However, at this dose level it neither had any adverse effect on vaginal tissue proliferation nor did it cause in situ apoptosis as evident from PCNA staining and TUNEL assay. Fertility and fecundity were restored 4-15 days after withdrawal of CAD application. At dose level 10 times that of its spermicidal MEC (minimum effective concentration), CAD did not block the growth of <it>Lactobacillus</it>, although the size of individual colony was marginally reduced. However, growth of the pathogenic fungus <it>Candida albicans </it>was completely inhibited with 20 mg/ml of CAD.</p> <p>Conclusion</p> <p>The overall result evolved from the study strengthens the candidature of CAD as a safe microbicidal spermicide. It is almost non-irritant to rabbit skin and rat vaginal tissues at doses 10 fold higher than its hemolytic index. The effect of CAD on <it>Lactobacillus </it>culture was not highly encouraging but it prevented the growth of the fungal pathogen <it>Candida albicans </it>at 20 mg/ml of CAD.</p

Synthesis and Characterization of Furo[3,2-h]Quinoliniums as Potent Non-Detergent Spermicides

7-Aryl substituted furo[3,2-h]quinoliniums have been synthesised in two steps from 5-chloro-8-hydroxy-7- iodo-quinoline through a tandem Sonogashira alkynylation-cyclization pathway using aryl acetylenes followed by quaternisation reaction with alkyl halides under microwave irradiation. The compounds have been characterized spectroscopically and assessed for their sperm-immobilizing efficacy in vitro by modified Sander–Cramer test. Most of the derivatives showed potent spermicidal effect with minimum effective concentration (MEC) ranging from 125�g/ml – 1mg/ml. The results were further confirmed by double fluoroprobe staining with syber14/PI (Propidium Iodide). The mode of spermicidal action was assessed by (a) Hypo-osmotic swelling tests and (b) Scanning electron microscopy. The compounds have been found to be nontoxic to lactobacillus in 36 hours of culture whereas mild to moderately effective on common vaginal pathogens. Taken together it can be inferred that the water-soluble salts prepared from facile technique are potential candidates for spermicides and could further be utilized for the preparation of vaginal contraceptives

Saponin Induced Clouding Behavior of Triton X-100 and Methylcellulose

The clouding behaviors of the surfactant p-tert-octylphenoxypolyoxyethylene ether (TX-100) and the water soluble polymer methylcellulose (MC) have been investigated in presence of two saponins, saponin-I (mixture of acaciaside A, acaciaside B, proacaciaside-I, proacaciaside-II, and acaciamine) and saponin-II (mixture of mimusopin and mimusopsin). The saponins have been observed to significantly prevent the clouding of both TX-100 and MC at low concentrations. Besides presenting the cloud points at different concentrations of the saponins, the energetics of the clouding process in terms of the solubilities of TX-100 and MC have also been determined

Efficient Synthesis of Novel Tetrahydropyrrolo[30,40:3,4]Pyrrolo[2,1-a] Isoquinoline Derivatives via a Simple and Convenient MCR in Aqueous Micellar System

A simple and efficient one-pot three component synthesis of tetrahydropyrrolo[30,40:3,4]pyrrolo[2,1- a]isoquinoline-9,11-dione derivatives has been achieved from variously substituted isoquinolines, 2- bromo acetophenone and N-aryl maleimide derivatives in an aqueous micellar medium. The synthesis represents an environmentally benign alternative to classical method

Indolylquinoline derivatives are cytotoxic to Leishmania donovani promastigotes and amastigotes in vitro and are effective in treating murine visceral leishmaniasis

A wide variety of biologically active compounds contain indole and quinoline nuclei. Some novel indolylquinoline derivatives were synthesized from indole by Friedel-Crafts acylation reaction. Out of the four derivatives tested, 2-(20-acetamidobenzyl)-3-(39-indolylquinoline) (C) had no effect on the promastigotes or amastigotes of Leishmania donovani in vitro. The remaining three analogues, 2-(20-dichloroacetamidobenzyl)-3-(39-indolylquinoline) (A), 2-(20- chloroacetamidobenzyl)-3-(39-indolylquinoline) (B), and 2-(20-aminobenzyl)-3-(39-indolylquinoline) (D), inhibited the growth of L. donovani promastigotes in vitro and were cytotoxic to both the promastigote and amastigote forms of the parasite. These three derivatives were also effective in eliminating L. donovani amastigotes from BALB/c mouse peritoneal macrophages in vitro. One indolylquinoline derivative [A] was used to treat established visceral leishmaniasis in BALB/c mice. This compound was significantly more effective than sodium antimony gluconate (SAG) in reducing the splenic parasite load at a much lower concentration (5% of SAG). Our results suggest that indolylquinoline derivatives may be exploited as antileishmanial agents

A Novel Approach for the One-Pot Synthesis of Linear and Angular Fused Quinazolinones

A convenient and inexpensive one step methodology has been developed for the synthesis of linear and angular fused quinazolinones. The protocol, which uses amino heterocycles and o-bromo benzyl/naphthyl bromides as reactants, CuI as catalyst, Cs2CO3 as base, L-proline as ligand, and DMF as solvent, proceeds via nucleophilic aromatic substitution of the N-heteroaromatic cationic intermediate followed by in situ aerial oxidation at the benzylic position to the quinazolinone scaffold

A Triterpenoid Saponin Possessing Antileishmanial Activity from the Leaves of Careya Arborea

Bioguided-fractionation of the methanol extract of the leaves of Careya arborea led to isolation of a triterpenoid saponin, designated arborenin, and characterized as 3-O-b-D-glucopyranosyl(1!2)-b-D-glucopyranosyl-2a,3b-dihydroxy-taraxast-20-en-28-oic acid (1), together with desacylescin III (2). The structures were determined on the basis of extensive 2D NMR spectroscopic analysis. The saponin showed in vitro antileishmanial activity against Leishmania donovani (strain AG 83)

Synthesis of Biaryl Pentacyclic Quinolonoquinoxalino-Oxazocines in Aqueous Medium Using Amberlite IRA 402(OH)

Amberlite IRA 402(OH) effectively mediates biarylation via Suzuki–Miyaura cross-coupling reaction on complex systems such as dihalo quinolonoquinoxalino-oxazocine

Facile Synthesis of Tricyclic Oxazino- or Oxazepino-Fused Tetrahydroquinolines via Intramolecular Reductive Amidation

Reductive cyclization of w-(8-quinolyloxy)alkyl esters by zinc in acetic acid is shown to constitute a convenient methodology for the synthesis of oxazino- or oxazepino-fused tetrahydroquinolines. It is operationally simple, requires a short reaction time, and provides excellent yields

Electron Density of Two Bioactive Oligocyclic Indole and Oxindole Derivatives Obtained from Low-Order X-Ray Data and Invariom Application

For two indole and oxindole bioactive molecules, low-order room-temperature X-ray data were used to generate aspherical electron density (ED) distributions by application of the invariom formalism. An analysis of the ED using the quantum theory of atoms in molecules (QTAIM) was carried out, which allowed for quantitatively examining bond orders and charge separations in various parts of the molecules. The inspection of electrostatic potentials (ESPs) and Hirshfeld surfaces provided additional information on the intermolecular interactions. Thus, reactive regions of the molecules could be identified, covalent and electrostatic contributions to interactions could be visualized, and the forces causing the crystal packing scheme could be rationalized. As the used invariom formalism needs no extra experimental effort compared to routine X-ray analysis, its wide application is recommended because it delivers information far beyond the normally obtained steric properties. In this way, complementary contributions to drug design can be given as is demonstrated for indoles in this study, which are involved in the metabolism of plants and animals as well as in cancer therapy