6-Bromoquinazoline Derivatives as Potent Anticancer Agents: Synthesis,Cytotoxic Evaluation,and Computational Studies

A series of 6-bromoquinazoline derivatives ( 5a – j ) were synthesized. Cytotoxic effectiveness of compounds was done against two cancerous cell lines (MCF-7 and SW480) by standard MTT method. Fortunately, all of the compounds showed desirable activity in reducing the viability of the studied cancerous cell lines with IC₅₀ value in the range of 0.53–46.6 μM. Compound 5b with a fluoro substitution at meta position of the phenyl moiety showed stronger activity than cisplatin with IC₅₀=0.53–1.95 μM. Studies on the hit compound ( 5b ) through apoptosis assay illustrated that it could induce apoptosis in MCF-7 cell lines in dose dependent manner. Molecular docking study was done to investigate the detailed binding modes and interactions with EGFR as a plausible mechanism. The drug- likeness was predicted. To survey the reactivity of compounds, DFT calculation was performed. Taken together, 6-bromoquinazoline derivatives, especially 5b can be considered as hit compounds to rational drug designing as antiproliferative agents.     

Identification and characterization of inulinases by bioinformatics analysis of bacterial glycoside hydrolases family 32 (GH32)

The glycoside hydrolase family contains enzymes that break the glycosidic bonds of carbohydrates by hydrolysis. Inulinase is one of the most important industrial enzymes in the family of Glycoside Hydrolases 32 (GH32). In this study, to identify and classify bacterial inulinases initially, 16,002 protein sequences belonging to the GH32 family were obtained using various databases. The inulin-effective enzymes (endoinulinase and exoinulinase) were identified. Eight endoinulinases (EC 3.2.1.7) and 4318 exoinulinases (EC 3.2.1.80) were found. Then, the localization of endoinulinase and exoinulinase enzymes in the cell was predicted. Among them, two extracellular endoinulinases and 1232 extracellular exoinulinases were found. The biochemical properties of 363 enzymes of the genus Arthrobacter, Bacillus, and Streptomyces (most abundant) showed that exoinulinases have an acid isoelectric point up to the neutral range due to their amino acid length. That is, the smaller the protein (336 aa), the more acidic the pI (4.39), and the larger the protein (1207 aa), the pI is in the neutral range (8.84). Also, a negative gravitational index indicates the hydrophilicity of exoinulinases. Finally, considering the biochemical properties affecting protein stability and post-translational changes studies, one enzyme for endoinulinase and 40 enzymes with desirable characteristics were selected to identify their enzyme production sources. To screen and isolate enzyme-containing strains, now with the expansion of databases and the development of bioinformatics tools, it is possible to classify, review and analyze a lot of data related to different enzyme-producing strains. Although, in laboratory studies, a maximum of 20 to 30 strains can be examined. Therefore, when more strains are examined, finally, strains with more stable and efficient enzymes were selected and introduced for laboratory activities. The findings of this study can help researchers to select the appropriate gene source from introduced strains for cloning and expression heterologous inulinase, or to extract native inulinase from introduced strains.     

Hormonally active nontransformed human ovarian cell culture from oophorectomy specimens: methods of development and initial characterization

We repeatedly established a nontransformed steroidogenically active human ovarian cell culture derived from oophorectomy specimens. The cells maintained steroidogenic activity for 3-5 passages (6-8 weeks) and responded to stimulation by insulin and gonadotropin. With pregnenolone as substrate, LH stimulated progesterone production up to 124% and FSH up to 121%. Insulin alone stimulated progesterone production up to 135%, in the presence of LH up to 191%, and in the presence of FSH up to 170%. With dehydroisoandrosterone (DHA) as substrate, insulin alone stimulated testosterone production up to 117%, and in the presence of LH (but not FSH) up to 125%. With androstenedione as substrate, insulin alone stimulated estradiol production up to 133%, FSH alone up to 188%, and LH with insulin up to 217%. With progesterone as substrate and in the presence of LH (but not FSH), 17-alpha-hydroxylase activity was stimulated up to 131%. With DHA as substrate and in the presence of LH, 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) activity was stimulated up to 139%. With androstenedione as substrate, insulin alone stimulated aromatase activity up to 202%, LH up to 208%, and FSH up to 251%. Under the same conditions, in the presence of LH and insulin, aromatase activity was stimulated up to 342%, and in the presence of FSH and insulin, up to 318%. With testosterone as substrate, insulin alone stimulated aromatase activity up to 122%. With testosterone as substrate, in the presence of LH and insulin, aromatase activity was stimulated up to 136%, and in the presence of FSH and insulin, up to 156%. Immunocytochemistry studies directly confirmed presence of aromatase and 3-beta-HSD in these cultured cells. We conclude that a steroidogenically active nontransformed long-term human ovarian cell culture can be repeatedly established from oophorectomy specimens, providing uninterrupted supply of cultured human ovarian cells for a variety of studies of ovarian physiology.     

Age and parasitism status of Tuta absoluta eggs alter the foraging responses of the predator Nabis pseudoferus

We studied the effect of Trichogramma brassicae Bezdenko (Hymenoptera: Trichogrammatidae) parasitism of Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) eggs on the foraging behavior of Nabis pseudoferus Remane (Hemiptera: Nabidae) feeding on T. absoluta eggs of different ages. Older parasitized eggs (48–72 h old) were rejected after probing with the probosis. A separate experiment showed that probing did not harm developing parasitoids. Bugs greatly reduced their feeding times on older parasitized eggs and spent more time grooming and probing eggs and leaves. Predators exhibited a type III functional response to 24 h-old eggs, but a type II response to older eggs, whether parasitized or not. 24 h-old eggs suffered higher attack rates, and required less handling time than older eggs. Although the predatory efficiency of N. pseudoferus was reduced in the presence of parasitized eggs, the partial refuge enjoyed by T. brassicae in older eggs may permit an additive impact on the pest, and should facilitate the joint augmentation of both species against T. absoluta.

     

Prevalence of cytomegalovirus infection and its role in total immunoglobulin pattern in Iranian patients with different subtypes of multiple sclerosis

Multiple sclerosis (MS) is the most common autoimmune disease characterized by multifocal areas of inflammatory demyelination within the central nervous system. Cytomegalovirus (CMV) has a complex pathobiology and in most cases is simply asymptomatic. There is some recent controversy over the role of CMV in the pathology of MS. The aim of this study was to evaluate active CMV infection and its effect on the humoral immunity in patients with MS. Serum, plasma, peripheral blood mononuclear cells (PBMCs), saliva and urine collected from MS patients (n=78) and healthy subjects (n=123) were screened for the presence of anti-CMV antibodies and CMV-DNA by nephelometric and PCR methods. Concentrations of total antibodies in MS subtypes were measured using both nephelometric and enzyme linked fluorescent assay (ELFA) techniques. The results extend the observation of an increased frequency of CMV-DNA in patients, in contrast with controls (p<0.001). Furthermore, systemic CMV infections were found in 25.5% of patients and only 3.2% of controls (p<0.001). There was significant difference in the titers of anti-CMV IgG and total IgE in patient and controls (P<0.001). These results support the hypothesis that CMV may contribute to MS thought to establish systemic infection process and induce immune response.     

A Prospective Study of Selenium Concentration and Risk of Preeclampsia in Pregnant Iranian Women: a Nested Case–Control Study

Preeclampsia remains a leading cause of maternal and perinatal mortality and morbidity worldwide; however, its specific etiology still remains obscure. Some studies implicate poor maternal selenium status predisposing the mother to preeclampsia. This study was designed to determine changes in plasma selenium levels in women having preeclampsia as compared with those with normal pregnancy. In a nested case–control study, 650 normal primigravida in their first 24–28 weeks participated in the study. After 3 months of follow-up of all subjects, blood selenium levels were measured in 38 women presenting consecutively with preeclampsia and in 38 women having a normal pregnancy by atomic absorption spectrophotometry. Birth outcomes were recorded, such as gestational age at delivery, height, weight, birth head circumflex and 1-min Apgar score. Preeclampsia affects about 5.84 % of pregnancies, and in our study, there were no significant differences in age, anthropometric indices, and family history of preeclampsia between the preeclamptic and control groups. The selenium concentrations in plasma in women with preeclampsia were significantly lower as compared with those in women with normal pregnancy (70.63?±?21.41 versus 82.03?±?15.54 μg/L, p?<?0.05). Being in the bottom tertile of selenium concentration (less than 62.2 μg/L) was associated with greater risk of preeclampsia in pregnant women. The reduced selenium in the maternal circulations observed in the preeclamptic mothers support the hypothesis that insufficient selenium concentration may be a contributing factor to the pathophysiological mechanisms associated with preeclampsia, and optimizing the dietary selenium intake through supplementation could produce demonstrable clinical benefits.     

Lethal and sublethal effects of spiromesifen,spirotetramat and spirodiclofen on Tetranychus urticae Koch (Acari: Tetranychidae)

Lethal and sublethal effects of spirotetramat, spiromesifen and spirodiclofen were assessed on Tetranychus urticae Koch. Leaf disc bioassay was used in all experiments. In this study, toxicity of these compounds was tested on T. urticae eggs and adults. Ovicidal activity was observed in all of the compounds tested, but only spirodiclofen was considerably effective against adult mites. Up to 24?h-old adult females were placed on leaf discs treated with sublethal concentrations (LC₁₀ or LC₂₅). Twenty-four hours after exposure to treated discs, 20 females showing no visible symptoms of poisoning were transferred to untreated leaf discs. The leaf discs were changed daily for up to five days. The number of eggs laid during this period was recorded. The survival rate, total number of laid eggs per female and egg hatching rate were calculated. All above-mentioned parameters were slightly lower in treated females compared with controls.     

Sexual dimorphism of the European Pond Turtle,Emys orbicularis (Linnaeus, 1758), in Anzali Lagoon,Iran (Reptilia: Emydidae)

The morphometric characteristics of the European Pond Turtle, Emys orbicularis, were studied at Anzali lagoon on the southern coast of the Caspian Sea. Males were on average (N=249) with 272.0?g significantly lighter than females with 447.0?g, and average carapace length was significantly smaller (123.0?mm in males, 139.0 in females). Females exceeded males also in all other studied characters (carapace width, plastron length, plastron width, and scute height). The sex ratio of male to female was 1 to 1.03, and the comparison of total tail length and cloaca-tail tip length revealed a difference between the position of the cloaca in both sexes, a character useful for sex determination in this species.