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A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin (

Visceral leishmaniasis (VL) is a vector–borne disease transmitted by Phlebotomine sandflies, with up to 350 million people are at risk of developing infection globally. VL has a severe influence on the impoverished and undeveloped populations among several subcontinents. Early and accurate diagnosis and treatment remain crucial to the management of VL, which still depends on vector control. The present chapter objectives are to provide an overview of visceral leishmaniasis and to raise knowledge of the most recent progress in this condition’s management, treatment, and prevention. Additionally, this chapter could be helpful for comprehending the difficulties and knowledge gaps in eliminating this protozoan disease as well as for learning the planning lessons from the global management of diseases like malaria and tuberculosis.

To study the correlation of cytogenetic and molecular abnormalities on induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL).Analytical study.Department of Haematology, Armed Forces Institute of Pathology (AFIP), from March 2021 to August 2021.Patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia were inducted. Patients aged less than 1 year and more than 18 years were excluded from the study. The diagnosis was based on morphology, cytochemistry, flow cytometry, and cytogenetic/molecular analysis. Risk stratification was done on the basis of age, TLC, and cytogenetic/molecular defects. The UKALL 2011 protocol was used for treatment with regimen-A for standard risk and regimen-B for high-risk patients. Bone marrow was repeated on day 29 of induction therapy and blast percentage was assessed to establish post-induction remission. Association between cytogenetic / molecular abnormalities and post-induction remission status was analysed using chi-square test.There were total 142 patients with mean age of 6.4 + 3.6 years and a male- to-female ratio of 2.7:1. Immunophenotyping revealed 85.9% cases as B-cell ALL and 14.1% as T-cell ALL. The most frequent cytogenetic and molecular abnormalities were hyperdiploidy (19%), t(9;22)/BCR-ABL1(p190) (10.6%), complex karyotype (5.6%), E2A-PBX1 (8.5%), and TEL-AML1 (4.9%). A total of 127/142 (89.4%) achieved haematological remission after induction therapy with two deaths during induction therapy (1.4%). Post-induction remission rate in patients with favorable cytogenetic/molecular defects was 100% and in children with bad prognostic changes, the rate of remission was 69.2%. Chi-square test showed a significant association between cytogenetic/molecular abnormalities and post-induction remission (p-value0.001).Cytogenetic and molecular abnormalities have a significant association with post-induction remission in children with acute lymphoblastic leukaemia.Acute lymphoblastic leukaemia, Cytogenetics, Chemotherapy, Induction, Remission.

An expeditious method for the synthesis of monosaccharides and disaccharides possessing 3-oxo-glycal units is revealed. Several monosaccharides and disaccharide-derived glycals are converted to the corresponding hexenuloses in three steps involving halo-alkoxylation, dehydrohalogenation, and ketalyzation reactions. A number of 3-oxo-glycals are synthesized to show the methodology's importance and generality. Further, the protocol is successfully applied to synthesize a rare-sugar disaccharide donor unit present as part of the trisaccharide moiety in the reported natural product, versipelostatin.

Nitro aromatic/nitrophenols have been widely distributed in nature and are mostly isolated from marine microorganisms and had shown a broad spectrum of anti–microbial activities against a wide range of microbial pathogens. The objective of the present work is to Synthesize some new 1,2,3–triazole tethered nitroguiacol ethers and evaluated of their anti–bacterial and anti–fungal activities. A focused library of 1,2,3-triazole tethered nitroguiacol ethers were prepared by employing Cu (I) catalyzed click chemistry reaction and evaluated for their antimicrobial activities by broth microdilution method. Among the tested compounds, compounds 8e, 8f, 8g, and 8i exhibited broad–spectrum activity against selected pathogenic strains, with the MIC of 8 µg/mL for gram–positive bacteria (Staphylococcus aureus), 16 µg/mL for Pseudomonas aeruginosa (gram–negative bacteria), and Candida species, respectively. Future investigations with this class of compounds may lead to the development of potential candidates for antimicrobial drug discovery.Â

NorA efflux pump pertaining to the major facilitator superfamily (MFS) is known to play a key role in antibiotic and biocide resistance in Staphylococcus aureus (S. aureus). It accounts for the extrusion of antibiotics like fluoroquinolones (e.g. ciprofloxacin). Several compounds including synthetic and natural products have been identified as potential NorA efflux pump inhibitors (EPIs) and found to restore the antibacterial activity of antibiotics. However, none of the reported EPIs have reached to clinical approval probably due to their high toxicity profiles. Considering the NorA efflux pump inhibitory potential of capsaicin, a series of capsaicin-based 1,3,4 oxadiazole conjugates were prepared and evaluated for ciprofloxacin activity potentiating effect. Among the new capsaicinoids tested, 17i displayed a minimum effective concentration (MEC) of 12.5 µg/mL against NorA overexpressing S. aureus strain (SA1199B), whereas capsaicin showed MEC of 50 µg/mL. The kill kinetics curve for the combination showed that ciprofloxacin at a sub–inhibitory concentration (0.25 × MIC) was equipotent in effect, to its MIC. 17i has significantly decreased the ethidium bromide efflux confirming NorA inhibition as the mode of action. Mutation prevention concentration of the ciprofloxacin was reduced in combination with 17i. In silico studies revealed the binding efficiency and binding affinity of 17i with NorA. This compound may serve as a template for the further drug discovery.

Higher education Institution (HEIs) around the globe is presently experiencing imperative changes to how they cooperate with the understudies, administration, faculty members and students. The majority of these establishments Concentrate for the most part on approaches to decrease costs and be powerful in the way they react to customer needs, and in this way pick up an aggressive Feature. Many of institutions, the concept of customer relationship management (CRM) is one, especially the education market becomes more competitive. There is a strong system of customer relationship management can help organizations gain unexpected, but important, advantage in high market higher education competitive. Ultimately, all of these factors combine to provide students with a sense of greater value. Customer relationship management (CRM) is a terminology that represents a business strategy built around the concept of improving customer services. CRM aims to increase customer satisfactions and thus increases the business income. It has been observed that the CRM not exploited on a large scale among the under developing countries such as Pakistan, especially in the higher education institutions higher education institutions (HEIs).Our findings suggest that a clear understanding of student life cycle will be more likely to adopt CRM. We propose that a fit between the choice of CRM goal strategic versus transactional CRM and organizational factors will help determine the continuous adoption of CRM by higher education users. This study examines why the critical success factors of CRM implementation , which HIEs especially in the MUET In the Engineering University have look to implement CRM and help them achieve their goals system

The core functionality of Operating Systems (OSs) is to keep flow of processes or execution of system running. The OS enforces flow of execution and smooth running of processes through implementing several hardware techniques, software applications and algorithms. This paper discusses those techniques in detail. The functionality of OS from context switching level to hardware issues, threats and their solutions have been explained and examined. Thus, it helps to understand how flow of processes has been enforced in OSs through several basic level core steps to advanced third party applications

The exponentially development of the Internet, World Wide Web, and Electronic Commerce has altered the innovative techniques of selling and marketing about services and products. At the same time as consequences of improvement and the evolution of the electronic information assets of product and service sellers and service providers face countless novel challenges. In this research researchers have discovered major ingredients related to Product, Trust, Price and customer satisfaction in E-commerce Environment and recommended conceptual framework with the support of relationship of dependent and independents variable. Moreover Research has found that peoples who have more trust in electronic commerce they mostly involve themselves in e-commerce. In this paper researcher has collect data through questionnaire from more than 300 users and analyze data with the help of SPSS software

The blockchain is generally defined as publicly disclosed and linked ledger of online transactions that are performed in peer to peer network. Also, all the transactions executed in this public ledger are verified by the majority of the participants. Blockchain has brought a different approach to the data sharing and management. It has come up with the solutions to a number of problems that the digital world has been facing since long. Blockchain technology is highly efficient to transform a number of industries such as financial and non-financial ones.

Wireless Sensor Networks (WSN) has been remained most demanding field due to its application-specific characteristics. There are various applications for WSN and among them some well-known application parameters are energy consumption and life-span longevity for the sake of routing. Genetic Algorithm is a robust optimization technique and possesses the large-scale computational applications. This paper is an attempt to survey of all operational phases of a WSN namely, quality of service (QoS) in routing, clustering, network coverage and localization as well multiple sinks. Additionally, the paper also discusses Genetic Algorithm applications.

A well designed image database is very necessary for the recognition of any language and many of language of the world have their own database for the text recognition. In this paper we are presenting the comprehensive database for Sindhi Language which is highly demanding language of the Middle East countries. The database will consist of the many words, which are written by the many writers. This is novel approach for the creating and testing of Sindhi Text. This database contains the isolated characters as well as the text of Sindhi language. The database is consisting of the images of the handwritten text, ground truth information, boxes for the users writing and lines for the text recognition. Tools for the segmentation and creation of the database have been developed in MATLAB, which helps to extract the handwritten data from the designed forms. We developed the different forms for the collection of data from the different users. This database can be used by the other language which possesses the same characteristics of Sindhi Language.

The present study was designed to investigate the potency of hydroxychavicol on selected cutaneous human pathogenic fungi by the use of in vitro and in vivo assays and mechanistic characterization along with toxicological effects. Hydroxychavicol consistently displayed a fungicidal effect against all fungal species tested. Inoculum concentrations over the range of 104 to 107 CFU/ml did not significantly alter its antifungal potential and time–kill curve results revealed concentration–dependent killing. It also inhibited the growth of biofilm generated by Trichophyton mentagrophytes and Candida parapsilosis and reduced the preformed biofilms. Hydroxychavicol was highly effective in the treatment, and mycological eradication of an experimentally induced topical infection model of dermatophytosis (tinea corporis) and cutaneous candidiasis in guinea pigs, respectively. The mode of action of hydroxychavicol appears to originate from the disruption of cell membrane integrity. Administration of hydroxychavicol in mice at 500 mg per kg of body weight by orally produced no overt toxicity. The retention capacity of hydroxychavicol in vitro, in the presence of keratin has attributed to its in vivo effectiveness in the guinea pig model of topical infections. Furthermore, it is suggestive of its potential use as phytochemical for topical use in cutaneous fungal infections.

This study was undertaken to investigate the synergistic interaction between amphotericin B (AmB) and acteoside, isolated from the aerial parts of the shrub Colebrookea oppositifolia (Lamiaceae). Acteoside alone exhibited no intrinsic antifungal activity but showed a potent synergism in combination with AmB against selected pathogenic species, with fractional inhibitory concentration indices in the range of 0.0312-0.1562. The combination of acteoside at 3.12 and 12.5 µg ml(-1) with subinhibitory concentrations of AmB resulted in a potent fungicidal effect and also exhibited a significantly extended post-antifungal effect. Furthermore, the combination also reduced the minimum biofilm reduction concentration values of AmB (2-16-fold) in preformed biofilms of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. There was decreased viability of the cells, increased uptake of propidium iodide and enhanced leakage of 260 nm-absorbing material by Candida albicans cells when exposed to AmB in the presence of acteoside. The reason for potentiation is likely to be that the subinhibitory concentrations of AmB facilitated the uptake of acteoside, which resulted in increased killing of the fungal cells. Administration of acteoside in mice at up to 2000 mg (kg body weight)(-1) by the intraperitoneal or oral route produced no overt toxicity. The data presented here support synergism between acteoside and AmB, and it is therefore proposed that a prospective new management strategy for therapeutic application of this combination should be explored.

Hydroxychavicol isolated from the chloroform extraction of aqueous extract of Piper betle leaves showed inhibitory activity against oral cavity pathogens. It exhibited an inhibitory effect on all of the oral cavity pathogens tested (MICs of 62.5 to 500 μg/ml) with a minimal bactericidal concentration that was twofold greater than the inhibitory concentration. Hydroxychavicol exhibited concentration-dependent killing of Streptococcus mutans ATCC 25175 up to 4× MIC and also prevented the formation of water-insoluble glucan. Interestingly, hydroxychavicol exhibited an extended postantibiotic effect of 6 to 7 h and prevented the emergence of mutants of S. mutans ATCC 25175 and Actinomyces viscosus ATCC 15987 at 2× MIC. Furthermore, it also inhibited the growth of biofilms generated by S. mutans and A. viscosus and reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide by hydroxychavicol-treated cells of S. mutans and A. viscosus indicated that hydroxychavicol probably works through the disruption of the permeability barrier of microbial membrane structures. Hydroxychavicol also exhibited potent antioxidant and anti-inflammatory activities. This was evident from its concentration-dependent inhibition of lipid peroxidation and significant suppression of tumor necrosis factor alpha expression in human neutrophils. Its efficacy against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose suggests that hydroxychavicol would be a useful compound for the development of antibacterial agents against oral pathogens and that it has great potential for use in mouthwash for preventing and treating oral infections.

Evaluation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus.A library of piperine-derived compounds was evaluated for their potential to inhibit ethidium bromide efflux in NorA-overexpressing S. aureus SA 1199B. The active compounds were then individually combined with ciprofloxacin to study the potentiation of ciprofloxacin's activity.Based on the efflux inhibition assay, a library of 200 compounds was screened. Three piperine analogues, namely SK-20, SK-56 and SK-29, were found to be the most potent inhibitors of the NorA efflux pump. These inhibitors acted in a synergistic manner with ciprofloxacin, by substantially increasing its activity against both NorA-overexpressing and wild-type S. aureus isolates. These analogues were 2- to 4-fold more potent than piperine at a significantly lower minimal effective concentration. Furthermore, these inhibitors also significantly suppressed the in vitro emergence of ciprofloxacin-resistant S. aureus.A newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting.

Background Hydroxychavicol, isolated from the chloroform extraction of the aqueous leaf extract of Piper betle L., (Piperaceae) was investigated for its antifungal activity against 124 strains of selected fungi. The leaves of this plant have been long in use tropical countries for the preparation of traditional herbal remedies. Methods The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of hydroxychavicol were determined by using broth microdilution method following CLSI guidelines. Time kill curve studies, post-antifungal effects and mutation prevention concentrations were determined against Candida species and Aspergillus species "respectively". Hydroxychavicol was also tested for its potential to inhibit and reduce the formation of Candida albicans biofilms. The membrane permeability was measured by the uptake of propidium iodide. Results Hydroxychavicol exhibited inhibitory effect on fungal species of clinical significance, with the MICs ranging from 15.62 to 500 μg/ml for yeasts, 125 to 500 μg/ml for Aspergillus species, and 7.81 to 62.5 μg/ml for dermatophytes where as the MFCs were found to be similar or two fold greater than the MICs. There was concentration-dependent killing of Candida albicans and Candida glabrata up to 8 × MIC. Hydroxychavicol also exhibited an extended post antifungal effect of 6.25 to 8.70 h at 4 × MIC for Candida species and suppressed the emergence of mutants of the fungal species tested at 2 × to 8 × MIC concentration. Furthermore, it also inhibited the growth of biofilm generated by C. albicans and reduced the preformed biofilms. There was increased uptake of propidium iodide by C. albicans cells when exposed to hydroxychavicol thus indicating that the membrane disruption could be the probable mode of action of hydroxychavicol. Conclusions The antifungal activity exhibited by this compound warrants its use as an antifungal agent particularly for treating topical infections, as well as gargle mouthwash against oral Candida infections.