SYNTHESIS OF SOME NOVEL TRIAZOLE DERIVATIVES AS SCHIFF BASES AND THEIR ANTIMICROBIAL EVALUATION

Objective: This work involves the synthesis of some novel schiff base derivatives synthesized from p-amino benzoic acid.Methods: A series of 4-[4-(arylidene amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl]-benzoic acid complexes were synthesized from 4-(4-amino-5-mercapto-4H-[1, 2, 4] triazol-3-yl)-benzoic acid by reaction with different aromatic aldehydes. All the synthesized schiff base derivatives were characterized by using analytical techniques (FT-IR, 1H NMR and Mass spectroscopy). The title compounds were evaluated for antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Streptococcus pneumoniae) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and anti-fungal activity against (Candida albicans and Aspergillus niger).Results: Schiff base derivatives 5(a-h) were synthesized in good yields and showed antimicrobial activity, among them, compounds 5c, 5d, 5e and 5f were significantly active against gram positive, gram negative bacterial and fungal strains and rest of compounds showed moderate to weak activity.Conclusion: The Schiff base obtained showed variation in the antimicrobial and antifungal activity, based on the structure of the substituted aromatic aldehydes

Development of a novel HPTLC fingerprint method for simultaneous estimation of berberine and rutin in medicinal plants and their pharmaceutical preparations followed by its application in antioxidant assay

The present study was designed to develop and validate a high-performance thin-layer chromatography (HPTLC) system for the simultaneous quantitative determination of berberine and rutin in Tinospora cordifolia extract and their pharmaceutical preparations. Chromatographic development was done using a blend of n-hexane, ethyl acetate, glacial acetic acid and methanol (10:1.1:1.1:2.5, v/v) as the mobile phase. Detection was completed densitometrically at 254 nm. The RF estimation of berberine and rutin was observed to be 0.67 ± 0.02 and 0.47 ± 0.02, respectively. The developed HPTLC method was validated according to ICH guidelines; the method was specific, linear and accurate and can be used to determine berberine and rutin in marketed herbal preparations. The Tinospora cordifolia plant extract was further evaluated for antioxidant activity using HPTLC, and berberine was found to be more active than rutin during DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity. The method was found simple, rapid, accurate, specific and robust for the analysis of berberine and rutin in crude drug using the same method

Role of Serine/Threonine Kinase 11 (STK11) or liver kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome

Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers

Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders

Hypoxia-inducible factor (HIF): fuel for cancer progression

Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygenindependent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors

Pharmacological properties of bergapten: mechanistic and therapeutic aspects

Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.info:eu-repo/semantics/publishedVersio

Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1 alpha

Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients

Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113

The authors wish to make the following corrections to this paper [...]