ABSTRACT
HESA-A is a natural product containing herbal and marine animal substances, which has been patented in Iran. It has shown antioxidant, cytotoxic and anticancer effects. The aim of this study was to evaluate the teratogenic effects of HESA-A in mice. HESA-A (50, 100, 200, 400 and 800 mg/kg) was administered orally to pregnant mice on days 6 to 14 of gestation. Mouse reproductive developmental toxicity study was performed according to the ICH guideline. Embryos from the treated dam were sectioned and studied for external morphological abnormalities and skeletal malformations. HESA-A at two doses (400 and 800 mg/kg) slowed weight gain of pregnant mice. These two doses of HESA-A led to reduction in uterus weight (17% and 20% for the 400 and 800 mg/kg doses, respectively), increase in post-implantation resorption (150% and 200%, respectively), reduction in fetus weight (22% and 32%, respectively) and crown-lump length (15% and 19%, respectively). HESA-A at 400 and 800 mg/kg doses caused mild external and skeletal malformation significantly higher than the normal saline group. However, higher doses caused embryo malformations such as short limbs, spinal abnormalities, dermal cysts, microphtalmia and cleft palate. According to this study, only higher doses of HESA-A, which are 20 to 40 times higher than the usual therapeutic doses based on body surface conversion, may cause embryonic toxicity. This provides a reasonable safety margin for the use of HESA-A in pregnancy. Mechanisms of these abnormalities are not clear and need to be determined.
Subject(s)
Abnormalities, Drug-Induced/etiology , Maternal Exposure/adverse effects , Plant Preparations/toxicity , Teratogens/toxicity , Abnormalities, Drug-Induced/embryology , Animals , Body Weight/drug effects , Dose-Response Relationship, Drug , Female , Gestational Age , Iran , Lethal Dose 50 , Mice , Mice, Inbred BALB C , PregnancyABSTRACT
A new series of 5-(5-nitro-2-thienyl)-2-(piperazinyl, piperidinyl and morpholinyl)-1,3,4-thiadiazole derivatives(5a-g) have been synthesized and evaluated against Mycobacterium tuberculosis H37Rv as apart of TAACF TB screening program under direction of the US National Institute of Health, NIAID division. Primary screening was conducted at the single concentration, 6.25 mg/ml against Mycobacterium tuberculosis H37Rv (ATCC 27294) in BACTEC 12B medium using a broth microdilution assay, the Microplate Alamar Blue Assay (MABA). The minimum inhibitory concentration (MIC) determined for compounds demonstrating 90% growth inhibition in the primary screening. The tested compounds showed a varying degree of inhibitory activity (Inhibition = 0-100%). The most active compounds were 4-methyl and 4-benzoylpiperaxinyl analogues(5b and 5g) with the same MIC value of 3.13 micrograms/ml.
Subject(s)
Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Morpholines/chemical synthesis , Morpholines/pharmacology , Mycobacterium tuberculosis/drug effects , Piperazines/chemical synthesis , Piperazines/pharmacology , Piperidines/chemical synthesis , Piperidines/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology , Indicators and Reagents , Microbial Sensitivity TestsABSTRACT
The in vitro antimycobacterial activity of a new quinolone derivative, 1a containing 2-(2-furyl)-2-oxoethyl group at N-4 position of piperazine ring of Ciprofloxacin was tested for efficacy in vitro in TB-infected macrophage model (EC90 = 3.25 micrograms/ml and EC99 > 12.5 micrograms/ml). The MIC values of 1a were determined against M. tuberculosis strains resistant to Isoniazid (MIC = 1.56 micrograms/ml), Rifampin (MIC = 1.56 micrograms/ml), Ethambutol (MIC = 0.78 microgram/ml), Kanamycin (MIC = 0.78 microgram/ml) and Ciprofloxacin (MIC > 25 micrograms/ml). Furthermore, the MIC and selectivity index (SI) of 1a were evaluated against M. avium. Also, in this study the minimum bactericidal concentration (MBC) of 1a was determined against M. tuberculosis H37Rv (MBC = 6.25 micrograms/ml) and strain resistant to Rifampim (MBC = 25 micrograms/ml) and Isoniazid (MBC = 25 micrograms/ml).
Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Ciprofloxacin/analogs & derivatives , Ciprofloxacin/pharmacology , Mycobacterium tuberculosis/drug effects , Drug Resistance, Microbial , Microbial Sensitivity Tests , Mycobacterium avium/drug effectsABSTRACT
A series of N-substituted-piperazinyl-quinolones were synthesized and evaluated for in vitro antibacterial activity. Compounds with a 2-(2,4-dichlorophenyl)-2-oxoethyl group attached to the piperazine ring (5a-c) had similar antibacterial activity to the reference drugs, ciprofloxacin, norfloxacin and enoxacin against both Gram-positive and Gram-negative bacteria. The oximes 6a-c and 6g-i were almost less active than corresponding ketones against the tested microorganisms, however the 2,4-difluorophenyl analogues (6g-i) were more active than 2,4-dichlorophenyl derivatives (6a-c). If the hydrogen of oxime is replaced with a benzyl group (6d-f & 6j-l), in-vitro antibacterial activity was decreased against both Gram-positive and Gram-negative bacteria. Generally ciprofloxacin derivatives were more active than norfloxacin and enoxacin derivatives.
