SYNTHESIS AND UTILITY OF NEW POLYCYCLIC COMPOUNDS AS POTENTIAL ANTIMICROBIALS BASED ON CHROMENE MOIETY

Objective: The present research aims to synthesize some new polycyclic compounds including chromene moiety and study their antimicrobial activity. Methods: Several new polycyclic systems including chromene scaffold incorporated with pyridine, pyrimidine, imidazopyrimidine, and imidazodiazocine were achieved via condensation reaction of chromene derivative under the proper condition with various reagents namely; cyanothioacetamide, phenyl isothiocyanate, malononitrile, carbon disulfide, benzaldehyde, triethyl orthoformate, and 1,4-dichlorobutane. Moreover, a chlorodiazenyl chromene derivative was reacted with some substances possessing active–CH2-bridge such as ethyl cyanoacetate and malononitrile to end up with hydrazono compounds. Such compounds were eventually cyclized with hydrazine hydrate to form pyrazole and oxopyrazole derivatives. Moreover, compound 1 was treated with benzoyl acetone, and then followed by cyclization with malononitrile to provide the corresponding 2-amino14-(4-methoxyphenyl)-4-methy-5-phenyl-14H-benzo[5,6] chromeno [2,3H][1,6]naphthyridine-3-carbonitrile (20). Results: The results of the antimicrobial screening in vitro revealed that the inhibition zone (mm) of the synthesized compounds 1-3, 5 and 8 implied their optimum antibacterial activity, while the compounds 4, 6 and 9-13, 15 showed a moderate to weak antibacterial activity against multiple species of B. subtilis, S. aureus, E. coli and P. aeruginosa. In contrast, the compounds 1, 6, 11, 15 showed high antifungal activities against different species of A. flavinand C. albicans, while the other compounds exhibit a moderate to poor antifungal activity. Conclusion: It is remarkable that a series of chromene derivatives synthesized by a simple and available method leads to a molecule of promising antimicrobial activity. Further research is recommended to approve the importance of polycyclic systems for various applications

The effectiveness of some pesticides in the control of thrips and red spider mites on strawberry plants

This study was carried out in a private farm in Wardan, Giza governorate in Egypt during 2019 season on strawberry plants. The first experiment aimed to evaluate the effectiveness of different commercial products in cultivated land including Solo 24% SC (Bifenazate), Arbus 12% SC (Chlorfenapyr + Emamectin benzoate) , Concor 24% SC (Spirodiclofen), Excellent 1.9% EC (Emamectin benzoate) , Top9 (Chitosan 0.1%) , Biomectin 5% EC (Abamectin) and Congest 15% CS (Abamectin + Imidacloprid) in reducing the population densities of two spotted spider mite, Tetranychus uriticae Koch. on strawberry plants. According to general mean percentage of reduction in population of T. uriticae, data showed insignificant differences among the seven tested compounds whereas the mortality percentages were 85.94 %, 82.18%, 81.4%, 79.36%, 78.14%, 77.94% and 75.9%, respectively. From these results; it’s clear that Solo compound is the most effective compound and Congest is the lowest one. The other compounds ranged between them in controlling T. uriticae under these experimental conditions. The second experiment evaluated the effectiveness of different formulations in the nursery including Radiant (Spinetoram 12% Sc), Super Rigo (Naphthyl acetic acid – Chitosan), Top9 and Berna Star (Glyceryl stearate 32%) in reducing the population densities of western flower thrips, Frankliniella occidentalis (Pergande) on strawberry plants. According to general mean percentage of reduction in population of F. occidentalis, data showed significant differences among the four compounds. These compounds could be divided into three groups. The first group contained Radiant compound showing high mortality (63.5%). The second group contained Super Rigo and Top9 compounds showing moderate effect (46.44% & 34.3%), respectively. The third group contained Berna Star compound showing least effect (28.36%). From these results; it’s clear that the chemical compound Radiant is the most effective while the natural compound Berna Star is the lowest in controlling F. occidentalis under these experimental conditions

Clinical Profile of Non-Motor Symptoms in Patients with Essential Tremor: Impact on Quality of Life and Age-Related Differences

Background: Identifying the clinical phenotypes of non-motor symptoms (NMSs) of essential tremor (ET) among different populations is necessary due to their impact on the quality of life (QoL). This study aimed to investigate the clinical phenotype and impact of NMSs on QoL in Egyptian patients with ET. Methods: Thirty ET patients were compared to 30 matched controls. Subjects were evaluated by the Fahn-Tolosa-Marin Tremor Rating Scale, Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Pittsburgh Sleep quality Index, and the Short Form 36 Health Survey Questionnaire. Both groups were divided into two subgroups of younger (45 years, 16 patients) groups, to investigate age-related differences. Results: ET patients showed significantly worse cognition, depression, anxiety, sleep and NMSS domains (p < 0.001), compared to controls, that negatively affected and predicted QoL. Older patients had more cognitive impairment (p = 0.003) and worse sleep/fatigue (p = 0.032) and sexual functions (p = 0.006), compared to younger group. Discussion: The study supports that NMSs are integral part of ET, negatively affect QoL, and similarly affect younger and older patients. Therefore, NMSs should be explored for proper care of ET patients

SYNTHESIS, ANTICANCER ACTIVITY AND MOLECULAR DOCKING STUDY OF NOVEL 1, 3-DIHETEROCYCLES INDOLE DERIVATIVES

Objective: The present work aimed to synthesize some new 1, 3-diheterocyles indolyl derivatives and study their cytotoxic activity. In addition, explore the probability of the most promising antiproliferative compounds to inhibit TopoI enzyme theoretically via molecular docking study.Methods: Reaction of ethyl 2-(3-formyl-1H-indol-1-yl)acetate (1) with 2-cyanoacetic acid hydrazide, 3-amino-5-pyrazolone and 2'-acetyl-2-cyanoacetohydrazide in an equal molar ratio led to the formation of compounds 2, 6, 8 and 10, respectively, which in turn reacted with another molecule of 2-cyanoacetic acid hydrazide and/or 3-amino-5-pyrazolone (1:1 molar ratio) to give novel series of 1,3-dipyrazole indole derivatives 3, 7, 9 and 11, respectively. On the other hand, Knoevenagel condensation of 1 with malononitrile gave ethyl 2-(3-(2, 2-dicyanovinyl)-1H-indol-1-yl) acetate (11). Reaction of 11 with 2-cyanoacetic acid hydrazide, 3-amino-5-pyrazolone, hydrazine hydrate, urea, thiourea and/or guanidine yielded 1, 6-diaminopyridine 12, pyrano(2,3-c)pyrazole 14, pyrazole 16 and pyrimidine derivatives 18a-c, respectively. Reaction of the latter compounds with 3-amino-5-pyrazolone furnished a novel series of 1, 3-diheterocycle indole derivatives 13, 15, 17 and 19a-c, respectively. Ten new target compounds 3, 6, 8, 10, 13, 15, 17 and 19a-c were tested for in vitro antiproliferative activity against A-549, MCF7, HCT-116 and HEPG2 cancer cell lines. In addition, molecular docking study of the most promising antiproliferative compounds against human DNA Topoisomerase I (PDB ID: 1T8I) theoretically is discussed.Results: Compounds 3, 6, 8 and 17 showed potent in vitro antiproliferative activity. Docking scores of the latter compounds were observed better than co-crystalline ligand.Conclusion: Further work is recommended to confirm the inhibition of TopoI in a specific bioassay

In ovo protective effects of chicoric and rosmarinic acids against Thiacloprid-induced cytotoxicity, oxidative stress, and growth retardation on newly hatched chicks

Thiacloprid (TH) is a neonicotinoid insecticide employed in agriculture to protect fruits and vegetables against different insects. It showed different deleterious effects on the general health of non-target organisms including birds and animals, however, its developmental toxicity has yet to be fully elucidated. Chicoric (CA) and rosmarinic (RA) acids are polyphenolic compounds with a wide range of beneficial biological activities. In this study, the possible protective effects of CA and RA were investigated in chick embryos exposed in ovo to TH (1mg/egg) with or without CA (100 mg/egg) or RA (100 mg/egg) co-exposure. TH reduced the hatchling body weight, body weight/egg weight, and relative weight of bursa of Fabricius in the one-day-old hatchlings. Examination of the 7-day-old chicks revealed a decline in feed intake, daily weight gain, feed conversion ratio (FCR), and plasma levels of T3, T4, and growth hormone. Serum ALT, AST activities, and total cholesterol levels showed significant elevations. Hepatic MDA was increased with a reduction in SOD activity and GSH level and downregulation of the liver SOD and GST gene expression pattern. Serum IgG and IgM levels were reduced, and various histopathological alterations were noticed in the liver. Co-administration of CA or RA with TH mitigated the toxic effects on hatchlings. When both CA and RA are combined, they present a synergistic protective effect. CA and RA can be used as protective agents against TH toxicity as they improve growth performance and have hepatoprotective and immunostimulant effects in newly hatched chicks

Analphoid supernumerary marker chromosome characterized by aCGH and FISH as inv dup(3)(q25.33qter) de novo in a child with dysmorphic features and streaky pigmentation: case report

<p>Abstract</p> <p>Background</p> <p>Small supernumerary marker chromosomes (sSMC) occur in 0.075% of unselected prenatal and in 0.044% of consecutively studied postnatal cases. Individuals with sSMC present with varying phenotype, ranging from normal to extremely mild or severe depending on the chromosomal region involved, the euchromatic content present and degree of mosaicism. Except for chromosomes 15 and 22, the number of reported cases of sSMC is extremely small to provide us with a good genotype-phenotype correlation. Analphoid sSMC are even rarer. To our knowledge only eight cases of analphoid inversion-duplication 3q sSMC are reported so far.</p> <p>Results</p> <p>We describe here a one month old female child with several dysmorphic features and with a <it>de novo </it>analphoid supernumerary marker chromosome only in cultured skin fibroblast cells and not in lymphocytes. The marker was characterized as analphoid inversion-duplication 3q25.33-qter by oligo array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH) studies. The final skin fibroblast karyotype was interpreted as 47,XX,+der(3).ish inv dup(3)(qter-q25.33::q25.33-qter)(subtel 3q+,subtel 3q+) <it>de novo</it>.</p> <p>Conclusion</p> <p>In addition to the eight reported cases of analphoid inversion-duplication 3q supernumerary marker in the literature, this is yet another case of 3q sSMC with a new breakpoint at 3q25.33 and with varying phenotype as described in the case report. Identification of more and more similar cases of analphoid inversion-duplication 3q marker will help in establishing a better genotype-phenotype correlation. The study further demonstrates that aCGH in conjunction with routine cytogenetics and FISH is very useful in precisely identifying and characterizing a marker chromosome, and more importantly help in providing with an accurate genetic diagnosis and better counseling to the family.</p

Physiological and Neurobehavioral Disturbances Induced by Al2O3 Nanoparticle Intoxication in Nile Tilapia Fish: Benefits of Dietary Chamomile Essential Oil

Despite the usage of nanoparticles (NPs) is rapidly increasing, several experts have noted the risk of their release into ecosystems and their potential negative impacts on biological systems. However, the available studies on the neurobehavioral impacts of aluminum oxide nanoparticles (Al2O3NPs) on aquatic organisms are little. Hence, this study targeted to ascertain the harmful effects of Al2O3NPs on behavioral characteristics and genotoxic and oxidative damages in Nile tilapia fish. In addition, the beneficial role of chamomile essential oil (CEO) supplementation in reducing these effects was also investigated. In the current study, fish were distributed into 4 equal groups (n = 60 fish per group). The control group was fed a plain diet only, the CEO group received a basic diet complemented with CEO at a level of 2 mg/kg diet, the ALNP group received a basic diet and was exposed to an approximate concentration of 1/10th LC50 of ALNPs nearly 5.08 mg/L, and the combination group (ALNPs/ CEO group) received a basal diet coadministered with ALNPs and CEO at the aforementioned percentages. The findings revealed that O. niloticus exhibit neurobehavioral changes along with changes in the level of GABA, monoamines in the brain tissue, and serum amino acid neurotransmitters, besides a reduction of AChE and Na+/K+-ATPase activities. In addition to brain tissue oxidative damage with upregulation of proinflammatory and stress genes, such as HSP70 and caspase-3, supplementation of CEO significantly reduced the negative impacts of ALNPs. These results showed that CEO has neuroprotective, antioxidant, genoprotective, anti-inflammatory, and antiapoptotic properties in fish that have been exposed to ALNPs. Therefore, we advise its usage as a valuable addition to fish diet

Clinical and histopathological responses to bee venom phonophoresis in treating venous and diabetic ulcers: a single-blind randomized controlled trial

IntroductionChronic venous and diabetic ulcers are hard to treat that cause patients long time of suffering as well as significant healthcare and financial costs.PurposeThe conducted study was to evaluate the efficacy of bee venom (BV) phonophoresis on the healing of chronic unhealed venous and/or diabetic foot ulcers Also, to compare the healing rate of diabetic and venous ulcers.MethodologyThe study included 100 patients (71 males and 29 females) with an age range of 40-60 years' old who had chronic unhealed venous leg ulcers of grade I, grade II, or diabetic foot ulcers with type II diabetes mellitus. They randomly assigned into four equal groups of 25: Group A (diabetic foot ulcer study group) and group C (venous ulcer study group) who both received conservative treatment of medical ulcer care and phonophoresis with BV gel, in addition to group B (diabetic foot ulcer control group) and group D (venous ulcer control group) who both received conservative treatment of medical ulcer care and received ultrasound sessions only without BV gel. Wound surface area (WSA) and ulcer volume measurement (UVM) were used to assess the ulcer healing pre-application (P0), post-6 weeks of treatment (P1), and after 12 weeks of treatment (P2). In addition to Ki-67 immunohistochemistry was used to evaluate the cell proliferative in the granulation tissue of ulcers pre-application (P0) and after 12 weeks of treatment (P2) for all groups.ResultsThis research revealed a statistical significance improvement (p ≤ 0.0) in the WSA, and UVM with no significant difference between study groups after treatment. Regarding Ki-67 immunohistochemistry showed higher post treatment values in the venous ulcer group in comparison to the diabetic foot ulcer group.ConclusionBee venom (BV) provided by phonophoresis is effective adjuvant treatment in accelerating venous and diabetic foot ulcer healing with higher proliferative effect on venous ulcer.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT05285930

Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus

AIM: We examined the role that immunoglobulin GM 23 and KM allotypes—genetic markers of γ and κ chains, respectively—play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients.MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA –C genotyping was also done.RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P &lt; 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001).The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001).CONCLUSION: Our results didn’t support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies