Regiospecific synthesis of some novel N-nucleosides of 4-amino-5-substituted-1,2,4-triazole-3-thiones and their in-vitro antimicrobial activity

4-Amino-5-substituted-1,2,4-triazole-3-thiones were prepared by following two different reaction routes and comparing the effectiveness of using different reaction conditions. The coupling of aminotriazoles with acetylated α-bromo-D-glucose furnished protected N-nucleosides regiospecifically. The reagents used gave only one regioisomer N-glycosides not the other S-nucleosides. The protected nucleosides upon deacetylation using methanolic ammonia afforded deprotected products. The chemical structures of synthesized compounds were confirmed by FT-IR, 1H NMR, 13C NMR, mass spectroscopic and elemental analysis data. All of the synthesized compounds were tested against ten different gram positive and gram negative bacterial strains which exhibited moderate to good antibacterial activity. The deprotected nucleosides portrayed high antibacterial activity than 4-amino-5-substituted-1,2,4-triazole-3-thiones and protected nucleosides against selected bacteria

Sputtering Deposition

Hundreds of research papers on various elements of sputtering have been published. The goal of this chapter is to present different aspects of sputtering that have been observed when materials are exposed to intense ion beams. Sputtering deposition is a common physical vapor deposition technology that has benefits over the molecular beam epitaxy and pulsed laser deposition in order to produce films of large area for a variety of industrial applications. Sputtering deposition has a reputation for producing high-quality epitaxial coatings and complicated oxide super-lattices at a cheaper cost than other methods, and the resulting films have proven to be essential enablers of scientific advancement. The sputtering process is discussed in detail, as well as the design and basic operations of the sputtering system, the effects of low and high energy sputtering, and changes in sputtering performance as a function of both the sputtering gas composition and the incident ion mass, dose, energy and angle. Sputtering deposition’s benefits, limits, and future trends are also discussed. Sputtering deposition is an important green technology for material production

Design, synthesis and screening of indole acetic acid-based tri-azo moieties as antioxidants, anti-microbial and cytotoxic agents

Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski’s rule of five. 5b showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50 μg/mL concentration. Compounds showed antibacterial activity against various tested strains. 5e and 5f showed a minimum inhibitory concentration (MIC) value of 3.12 μg/mL for P.aeruginosa and K.pneumoniae, respectively. In the antifungal assay, only 5e inhibited one strain with a zone of inhibition >6 mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; 5c, 5d, and 5f exhibited LC50 =5.7 μg/mL. In the protein kinase inhibition assay, 5a, 5b, and 5g demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5–10.5 mm for the bald one and 6–7.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area

Pattern of unnatural deaths during COVID-19 lockdown in comparison with deaths reported during 2019 in Sahiwal city

Background:  Lockdown, a social isolation restriction measure has a direct impact on covid-19 transmission but its effect on unnatural deaths remains unknown. Objective:  This study has been designed to observe the effects of covid-19 lockdown on unnatural deaths in Sahiwal by comparing with the same period in 2019. Study design: Descriptive retrospective study. Setting: The study was conducted in mortuary of DHQ Teaching Hospital Sahiwal attached with the Department of Forensic Medicine & Toxicology Sahiwal medical college, Sahiwal. Study Duration: Covid-19 lockdown period from 24th March 2020 to 9th May 2020 and the same period in 2019. Materials and Methods: This study includes 62 cases of unnatural deaths, out of which 23 Cases in 2019 and 39 cases in 2020. We have included age, sex, marital status, area of belonging, manner of death, and cause of death as variables in our study. Results: In total 62 cases, in 2019 there were 15 males and 8 females with a mean age of 37.30±19.55 years and in 2020, there were 27 males and 12 females with a mean age of 32.85±15.16 years. The age group in which most number of deaths occurred was 30-59 years (46.8%). In 2019 majority of victims died due to homicide 15(65.2%) while during the lockdown period 14 (35.9%) victims lost their lives in accidents. Firearm injuries were the cause of death in 11(47.8%) cases in 2019 while in the COVID 19 lockdown period the majority of cases 13 (33.3%) were those who died due to roadside accidents. Conclusions: We could not detect significant difference in the two periods examined with respect to sociodemographic factors, but manner of death was significantly affected

The Benzimidazole Derivatives, B1 (N-[(1H-Benzimidazol-2-yl)Methyl]-4-Methoxyaniline) and B8 (N-{4-[(1H-Benzimidazol-2-yl)Methoxy]Phenyl}Acetamide) Attenuate Morphine-Induced Paradoxical Pain in Mice

Despite being routinely used for pain management, opioid use is limited due to adverse effects such as development of tolerance and paradoxical pain, including thermal hyperalgesia and mechanical allodynia. Evidence indicates that continued morphine administration causes increased expression of proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α). The objectives of the present study were to determine the effects of B1 (N-[(1H-benzimidazol-2-yl)methyl]-4-methoxyaniline) and B8 (N-{4-[(1H-benzimidazol-2-yl)methoxy]phenyl}acetamide), benzimidazole derivatives, on thermal nociception and mechanical allodynia during repeated morphine (intraperitoneal; 5 mg/kg twice daily for 6 days)-induced paradoxical pain and TNF-α expression in the spinal cord in mice. Our data indicate that administration of benzimidazole derivatives attenuated morphine-induced thermal hyperalgesia and mechanical allodynia. Benzimidazole derivatives also reduced TNF-α expression in mice. Taken together, these results suggest that benzimidazole derivatives might be useful for the treatment of neuroinflammatory consequences of continued morphine administration and could be potential drug candidates for the management of opioid-induced paradoxical pain

Anti-hyperglycemic activity of Heliotropium strigosum (Boraginaecae) whole plant extract in alloxan-induced diabetic mice

Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce the blood glucose level of alloxan-induced diabetic mice.Methods: Preliminary phytochemical analysis was carried out using standard  procedures. Diabetes was induced in Balb/c mice by injecting alloxan (200 mg/kg i.p.). The crude methanol extract of Heliotropium strigosum (Hs.Cr, 30, 100 and 300 mg/kg doses) was administered daily to alloxan-induced diabetic mice for 15 days and its effect on fasting blood glucose levels, body weight and oral glucose tolerancewas evaluated. Two control groups (non-diabetic control and diabetic control)  received normal saline (0.2 ml). Metformin (500 mg/kg) was used as reference standard.Results: Heliotropium strigosum showed positive for the presence of alkaloids, tannins and flavonoids. The extract (30, 100 and 300 mg/kg) caused significant reduction in the fasting blood glucose level of alloxan-induced diabetic mice on days 5, 10 and 15 compared to diabetic control (p < 0.001). In this regard, the  anti-hyperglycemic effect compared to the reference (metformin). The extract also timedependently decreased the body weight of the treated animals as well as improved tolerance of the oral glucose overload.Conclusion: These results indicate that Heliotropium strigosum possesses  anti-hyperglycemic effect, reduces body weight and enhances the tolerance of  glucose overload in mice. Further studies are therefore required to determine its  feasiilty as an alternate herbal medicine in the management of diabetes in humans.Keywords: Heliotropium strigosum, Anti-hyperglycemic, Alloxan-induced diabetic mice, Blood glucose, Oral glucose tolerance, Body weigh

Clinical evaluation of patients suffering from breast cancer and determination of evolving treatment therapies and better strategies related to breast cancer

Abstract: Breast cancer is basically the lesion of female breast that may create from the connective tissue or epithelial cells of breast.Primary objective: The objective of study was to conduct a survey about the prevailing of rate of breast cancer in community of Rawalakot, Islamabad and local community and to find out strategies used for the diagnosis, treatment and prevention of breast cancer. Methods/Design: A well structure questionnaire including 35 questions about the history, sociodemograhic characteristics, diagnostic tools, treatment plans and prevention methods has been prepared and circulated among the patients of breast cancer through survey. Setting: Study was conducted in Rawalakot and Islamabad Pakistan Participants: 50 participants were involved Intervention: The study was also conducted to communicate with larger community of breast cancer patients and to give them awareness related to initial diagnosis of this harmful disease. Primary Outcome Measures: This study was very very helpful in educated and non-educated community of the specific cities . Results: While conducting the research based on studies, it was found that about 68.84% patients has been report with the reoccurrence of breast cancer after surgery, 70% patients have been diagnosed with invasive type and 30% non-invasive type and 50% have been treated with hormonal therapy as continued treatment after surgery. Conclusion : Breast cancer variation among population or regional differences in the types have been attribute to the prevalence of major risk factors, availability and use of medical practices such as cancer screening, availability and quality of treatment, completeness of reporting and age structure.

Benzimidazole containing acetamide derivatives attenuate neuroinflammation and oxidative stress in ethanol-induced neurodegeneration

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Oxidative stress-induced neuroinflammation is the prominent feature of neurodegenerative disorders, and is characterized by a gradual decline of structure and function of neurons. Many biochemical events emerge thanks to the result of this neurodegeneration, and ultimately provoke neuroinflammation, activation of microglia, and oxidative stress, leading to neuronal death. This cascade not only explains the complexity of events taking place across different stages, but also depicts the need for more effective therapeutic agents. The present study was designed to investigate the neuroprotective effects of newly synthesized benzimidazole containing acetamide derivatives, 3a (2-(4-methoxyanilino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) and 3b (2-(Dodecylamino)-N-[1-(4-methylbenzene-1-sulfonyl)-1H-benzimidazol-2-yl] acetamide) against ethanol-induced neurodegeneration in the rat model. Both derivatives were characterized spectroscopically by proton NMR (1H-NMR) and carbon-13 NMR (13C-NMR) and evaluated for neuroprotective potential using different pharmacological approaches. In vivo experiments demonstrated that ethanol triggered neurodegeneration characterized by impaired antioxidant enzymes and elevated oxidative stress. Furthermore, ethanol administration induced neuroinflammation, as demonstrated by elevated expression of tumor necrotic factor (TNF-α), nuclear factor κB (NF-κB), cyclooxygenase-2 (COX2), and ionized calcium-binding adapter molecule-1 (Iba-1), which was further validated by enzyme-linked immunosorbent assay (ELISA). Treatment with 3a and 3b ameliorated the ethanol-induced oxidative stress, neuroinflammation, and memory impairment. The affinity of synthesized derivatives towards various receptors involved in neurodegeneration was assessed through docking analysis. The versatile nature of benzimidazole nucleus and its affinity toward several receptors suggested that it could be a multistep targeting neuroprotectant. As repetitive clinical trials of neuroprotectants targeting a single step of the pathological process have failed previously, our results suggested that a neuroprotective strategy of acting at different stages may be more advantageous to intervene in the vicious cycles of neuroinflammation

Pharmacokinetics of Caffeic Acid from Methanol Seed Extract of Syzygium cumini L in Rats

Purpose: To describe caffeic acid-based pharmacokinetics of methanol extract of seed of Syzygium cumini L. in rats.Methods: A dose of the extract (500 mg, equivalent to 37.135 mg caffeic acid) was administered orally to 6 male Wister rats, weighing 200 ± 10 g. Blood samples (0.5 mL), collected from the tail vein at 0, 15, 30, 60, 120, 240 and 720 min, were processed and analyzed using high performance liquid chromatography and detected with florescent light detector (FLD).Results: Following the administration of the extract, caffeic acid achieved maximum plasma concentration (5.96 ± 0.49 μg/mL) in 1.0 h which was also the time to achieve maximum concentration (Tmax). Mean resident time (MRT) and half-life (t1/2) were 4.092 ± 0.94 h and 0.14 ± 0.01 h, respectively.Conclusion: The results indicate that absorption of caffeic acid from the oral route is fast, but lower amounts are absorbed. The method developed for the extraction of caffeic acid from the plasma and HPLC determination may be useful in establishing phyto-bioequivalence between Syzygium cumini seed products.Keywords: Caffeic acid, Pharmacokinetics, Syzygium cumini, Phytobioequivalence, Absorptio