Different Strategies Targeting Gut Microbiota for the Management of Several Disorders: A Sustainable Approach.

BACKGROUND: A potential limelight is flashed on the Gut Microbiota (GM) in the human body, which confers additional psychological as well as physiological attributes to health. Other than just occupying a wide portion of the gastrointestinal tract, it also plays numerous functions in the systems of the body. Gut Microbiota is largely responsible for a considerably vast array of conditions such as obesity, diabetes ,other metabolic disorders, and cardiovascular disorders. Strategies targeting the gut microbiota have been proposed as a promising approach for the management of these disorders. OBJECTIVE: This review aims to summarize the different strategies targeting the gut microbiota for the management of several disorders and to highlight the importance of a sustainable approach. METHODS: A comprehensive literature search was conducted using various databases between 2008 and 2022 that focused on the use of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, dietary interventions, and antibiotics. RESULTS: Different strategies targeting the gut microbiota for the management of several disorders were identified, including probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and dietary interventions. Modification in diet and lifestyle, allowing favorable microbiota growth in the stomach, intake of prebiotics and probiotics, and fecal microbiota transplantation are amongst the widely accepted recent approaches allowing the application of GM in the field of treatment. CONCLUSION: Although considerable steps in enhancing and understanding the mechanism of treatment with the help of gut microbiota are under progress, much diversified and elaborate research must be conducted in order to enhance and implement the use of GM with high effectiveness.

An Insight into the Development of Potential Antidiabetic Agents along with their Therapeutic Targets.

Diabetes is a metabolic disorder that has been reported to increase the mortality rate worldwide. About 40 million people across the globe suffer from diabetes, with people living in developing countries being affected the most due to this deadly disease. Although the therapeutic management of hyperglycaemia can treat diabetes, metabolic disorders associated with this disease are a greater challenge in its treatment. Hence, potential strategies to treat hyperglycaemia and its side effects are needed. In this review, we have summarized several therapeutic targets, like dipeptidyl peptidase-4 (DPP-4), glucagon receptor antagonists, glycogen phosphorylase or fructose-1,6- biphosphatase inhibitors, SGLT inhibitors, 11beta-HSD-1 inhibitors, glucocorticoids receptor antagonists, glucose-6-phosphatase and glycogen phosphorylase inhibitors. These targets can help in designing and developing novel antidiabetic agents.

Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR.

Prostate cancer is a disease that is affecting a large population worldwide. Androgen deprivation therapy (ADT) has become a foundation for the treatment of advanced prostate cancer, as used in most clinical settings from neo-adjuvant to metastatic stage. In spite of the success of ADT in managing the disease in the majority of men, hormonal manipulation fails eventually. New molecules are developed for patients with various hormone-refractory diseases. Advancements in molecular oncology have increased understanding of numerous cellular mechanisms which control cell death in the prostate and these insights can lead to the development of more efficacious and tolerable therapies for carcinoma of the prostate. This review is focused on numerous therapies that might be a boon for prostate therapy like signaling inhibitors, vaccines, and inhibitors of androgen receptors. Along with these, various bioactive molecules and their derivatives are highlighted, which act as potential anti-prostate cancer agents. This article also emphasized the recent advances in the field of medicinal chemistry of prostate cancer agents.

Therapeutic Management with Repurposing Approaches: A Mystery During COVID-19 Outbreak.

The ubiquitous pandemic that emerged due to COVID-19 affected the whole planet. People all over the globe became vulnerable to the unpredictable emergence of coronavirus. The sudden emergence of respiratory disease in coronavirus infected several patients. This affected human life drastically, from mild symptoms to severe illness, leading to mortality. COVID-19 is an exceptionally communicable disease caused by SARS-CoV-2. According to a genomic study, the viral spike RBD interactions with the host ACE2 protein from several coronavirus strains and the interaction between RBD and ACE2 highlighted the potential change in affinity from the virus causing the COVID-19 outbreak to a progenitor type of SARS-CoV-2. SARS-CoV-2, which could be the principal reservoir, is phylogenetically related to the SARS-like bat virus. Other research works reported that intermediary hosts for the transmission of viruses to humans could include cats, bats, snakes, pigs, ferrets, orangutans, and monkeys. Even with the arrival of vaccines and individuals getting vaccinated and treated with FDA-approved repurposed drugs like Remdesivir, the first and foremost steps aimed towards the possible control and minimization of community transmission of the virus include social distancing, self-realization, and self-health care. In this review paper, we discussed and summarized various approaches and methodologies adopted and proposed by researchers all over the globe to help with the management of this zoonotic outbreak by following repurposed approaches.

A Rationalized Approach to Design and Discover Novel Non-steroidal Derivatives through Computational Aid for the Treatment of Prostate Cancer.

BACKGROUND: Prostate cancer is one of the most prevalent cancers in men, leading to the second most common cause of death in men. Despite the availability of multiple treatments, the prevalence of prostate cancer remains high. Steroidal antagonists are associated with poor bioavailability and side effects, while non-steroidal antagonists show serious side effects, such as gynecomastia. Therefore, there is a need for a potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effects, and minimal side effects. OBJECTIVE: This current research work focused on identifying a novel non-steroidal androgen receptor antagonist through computational tools, such as docking and in silico ADMET analysis. METHODS: Molecules were designed based on a literature survey, followed by molecular docking of all designed compounds and ADMET analysis of the hit compounds. RESULTS: A library of 600 non-steroidal derivatives (cis and trans) was designed, and molecular docking was performed in the active site of the androgen receptor (PDBID: 1Z95) using AutoDock Vina 1.5.6. Docking studies resulted in 15 potent hits, which were then subjected to ADME analysis using SwissADME. ADME analysis predicted three compounds (SK-79, SK-109, and SK-169) with the best ADME profile and better bioavailability. Toxicity studies using Protox-II were performed on the three best compounds (SK-79, SK-109, and SK-169), which predicted ideal toxicity for these lead compounds. CONCLUSION: This research work will provide ample opportunities to explore medicinal and computational research areas. It will facilitate the development of novel androgen receptor antagonists in future experimental studies.

Marine-derived Natural Products as Anticancer Agents.

Cancer is a deadly human disease on the rise due to changes in lifestyle, nutrition, and global warming. Cancer is characterized by uncontrolled, disordered, and undesired cell division. About 60% of cancer medicines approved by the FDA are made from natural ingredients. Intensive efforts over the last decade to better understand the vast chemical diversity provided by marine life have resulted in an intriguing "marine pipeline" of potential anticancer clinical and preclinical treatments. The molecular targets of marine products as anticancer drugs, as well as different reported compounds acting on distinct targets, are the topic of this review.

Tetrazole: A privileged scaffold for the discovery of anticancer agents.

Carcinoma, characterized by abnormal growth of cells and tissue, is a ubiquitously leading cause of mortality across the globe due to some carcinogenic factors. Currently, several anticancer agents are commercially available in the global market. However, due to their resistance and cost, researchers are gaining more interest in developing newer novel potential anticancer agents. In the search for new drugs for clinical use, the tetrazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules. Among the various heterocyclic agents, tetrazole-containing compounds have shown significant promise in the treatment of a wide range of diseases, particularly cancer. Here, in this review, we focused on several synthetic approaches for the synthesis of tetrazole analogs, their targets for treating cancer along with the biological activity of some of the recently reported tetrazole-containing anticancer agents.

Emerging quinoline- and quinolone-based antibiotics in the light of epidemics.

Pandemics are large-scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Quinoline and quinolone antibiotics exhibit extensive activities approved by FDA in the treatment of the several ailments such as gastrointestinal infections, urinary tract infections, prostate inflammation, malaria, gonorrhea, skin infection, colorectal cancer, respiratory tract infections. These are active against both gram-negative and gram-positive bacteria. This basic core of quinoline and quinolone is vital due to its capability of targeting the pathogen causing disease and beneficial in treating the infectious disease. They inhibit the synthesis of nucleic acid of bacteria which results in the rupture of bacterial chromosome due to the interruption of enzymes such as DNA gyrase and topoisomerase IV. There are various quinoline and quinolone compounds that are synthetically derived by applying different synthesis approaches which show a wide range of pharmacological activities in several diseases. The most commonly used are fluoro, chloro, and hydroxychloro derivatives of quinoline and quinolone. These compounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life-threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID-19 (currently). In this chapter, the research and advancements of quinoline- and quinolone-based antibiotics in epidemic management are briefly discussed.

A new insight into the treatment of diabetes by means of pan PPAR agonists.

PPARs stand for 'peroxisome proliferator-activated receptors' and are ligand-activated transcription factors of nuclear hormone receptor superfamily. A list of the most commonly used single receptor PPAR agonists, that is α (alpha) PPAR agonists, ß/δ(beta/delta) PPAR agonists, γ(gamma) PPAR agonists, along with pan PPAR agents, that are being researched on, are marketed, are in clinical trials or are being studied for further derivative findings, has been listed. Type 2 diabetes constitutes about 90% of total diabetes cases. Pan PPAR ligands could very well pave the foundation for a new class of agents, that can act on all 3 PPAR receptors, and produce better effects in general, than the individual receptor-acting ligands or dual combination ligands (α/ γ). In this review paper, we have detailed various pan PPAR agonists that can be used to treat type 2 diabetes, which can generate potential derivatives as well.

Withdrawal Notice: Therapeutic Targets Underlying the Evolution of Po-tential Anti-Diabetic Agents: A Comprehensive Review

The article has been withdrawn at the request of the editor of the journal Current Diabetes Reviews due to incoherent content.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

A Critical Review on Recent Development of Techniques and Drug Targets in the Management of Breast Cancer.

BACKGROUND: The most documented illness affecting women overall is breast malignant growth. Since breast cancer disease is the most widely recognized threat in women, Since breast cancer disease is the most widely recognized threat in women, this review was done to provide data on the ongoing advancements in the medication focused on in the breast cancer regimen. Over the previous decades, it has been seen that different progressions have been made in the disclosure of new medications and treatments for treating breast malignancy and this is a direct result of the improved comprehension of the biologic heterogeneity of breast cancer, which has likewise permitted the advancement of increasingly compelling ways to deal with treating breast cancer. METHODS: We searched the scientific database using relevant keywords. Among the searched literature, only peer-reviewed papers were collected, which address our questions. The retrieved quality papers were screened and analyzed critically. The key findings of these studies are included along with the importance. RESULTS: The research in this review particularly includes the anti-breast cancer drugs, which accountfor the top largest market by sales in the pharmaceutical industry. Apart from these, natural and innovative therapies have emerged leading to better management of breast cancer. CONCLUSION: These recent developments have contributed to a more efficient and specific treatment protocol in breast cancer patients. Moreover, further investigation should be done in improving results for all the patients with breast cancer disease, particularly individuals who have advanced breast cancer and the issue of drug resistance, which also poses a threat to the successful development of targeted therapy in various subtypes of breast cancer, must also be considered.

An Overview of Computer-aided Drug Design Tools and Recent Applications in Designing of Anti-diabetic Agents.

BACKGROUND: In this fast-growing era, high throughput data is now being easily accessed by getting transformed into datasets which store the information. Such information is valuable to optimize the hypothesis and drug design via computer-aided drug design (CADD). Nowadays, we can explore the role of CADD in various disciplines like Nanotechnology, Biochemistry, Medical Sciences, Molecular Biology, etc. Methods: We searched the valuable literature using a pertinent database with given keywords like computer-aided drug design, anti-diabetic, drug design, etc. We retrieved all valuable articles which are recent and discussing the role of computation in the designing of anti-diabetic agents. RESULTS: To facilitate the drug discovery process, the computational approach has set landmarks in the whole pipeline for drug discovery from target identification and mechanism of action to the identification of leads and drug candidates. Along with this, there is a determined endeavor to describe the significance of in-silico studies in predicting the absorption, distribution, metabolism, excretion, and toxicity profile. Thus, globally, CADD is accepted with a variety of tools for studying QSAR, virtual screening, protein structure prediction, quantum chemistry, material design, physical and biological property prediction. CONCLUSION: Computer-assisted tools are used as the drug discovery tool in the area of different diseases, and here we reviewed the collaborative aspects of information technologies and chemoinformatic tools in the discovery of anti-diabetic agents, keeping in view the growing importance for treating diabetes.

Synthesis and evaluation of new 1,2,4-oxadiazole based trans- acrylic acid derivatives as potential PPAR-alpha/gamma dual agonist.

Diabetes is a ubiquitously a metabolic disorder and life-threatening disease. Peroxisome proliferator-activated receptors (PPARs) belong to the class of nuclear receptors which acts as transcription factors to regulate lipid and glucose metabolism. PPAR alpha/gamma dual agonists tend to corroborate the functions of both thiazolidinediones and fibrates and they hold substantial promise for ameliorating the type 2 diabetic treatments and providing potential therapeutic diabetic interventions. New 1,2,4-oxadiazole based trans- acrylic acid derivatives compounds possessing aryl/methylene linker in between pharmacophore head and lipophilic tail for dual PPAR-alpha/gamma agonists are studied. AutoDock Vina used for potential PPAR alpha/gamma dual agonists and 6 compounds 9a, 9g, 9 m, 9n, 9o, and 9r were identified comparable to PPAR gamma agonist Pioglitazone on the basis of their affinity scores and further their in-silico toxicity and in-silico ADME properties. The selected compounds showed better-calculated lipophilicity (iLogP) was found to be 0.92 to 3.19. Compound 9n and 9a were found to be most potent on both PPAR alpha and gamma receptors with EC50 of 0.07 ± 0.0006 µM, 0.06 ± 0.0005 µM and 0.781 ± 0.008 µM, 3.29 µM ± 0.03 respectively as better to pioglitazone having EC50 of 32.38 ± 0.2 and 38.03 ± 0.13 for both receptors. The in-vivo evaluation found to reduce the plasma glucose level and total cholesterol level significantly in diabetic rats compared to pioglitazone at 5 mg/kg/day dose for 7 days of treatment. Thus, trans- acrylic acid derivatives can be further developed as oral therapeutic agents for diabetic interventions as PPAR alpha/gamma dual agonists.

Current Strategies and Drug Targets in the Management of Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes is one of the major concerns worldwide which leads to increased level of blood glucose due to deficiency of insulin and the development of insulin resistance in diabetic individuals. Basically, its impact arises due to rapid urbanization, improper diet intake, and increasingly inactive lifestyle. Diabetic patients develop serious complications with the development of disease at later stages, such as obesity, the risk of stroke and heart failure. Globally, an estimated 422 million adults are living with type 2 diabetes mellitus. METHODS: We searched the scientific database using relevant keywords. Among the searched literature, only peer-reviewed papers were collected which addresses our questions. The retrieved quality papers were screened and analyzed critically. The key findings of these studies are included along with the importance. RESULTS: The quality research paper included in the review, particularly the antidiabetic drugs which account for the second largest market by sales in the pharmaceutical industry after cancer. So the research came up with several novel therapeutic targets for the management of type 2 diabetes, to produce newer generation antidiabetic drug by offering a new concept for developing new drug candidates. CONCLUSION: This review discusses the strategies and future perspectives in the management of type 2 diabetes mellitus particularly antidiabetic agents which are helpful for the betterment of diabetic patients.

A Retrospect Study on Thiazole Derivatives as the Potential Antidiabetic Agents in Drug Discovery and Developments.

BACKGROUND: Heterocycles containing thiazole, a moiety with sulfur and nitrogen is a core structure which is found in a number of biologically active compounds. The thiazole ring is notable as a component of the certain natural products, such as vitamin B1 (thiamine) and penicillins. Thiazole is also known as wonder nucleus and has uses in different biological fields. A number of new compounds contain heterocycle thiazole moieties, thus it is one of the important areas of research. METHODS: We searched the scientific database using relevant keywords. Among the searched literature only peer-reviewed papers were collected which addresses our questions. The retrieved quality research articles were screened and analyzed critically. The key findings of these studies were included along with their importance. RESULTS: The quality research articles included in this review were selected for the lifethreatening diseases i.e. diabetes, which is one of the serious issues all over the globe with an estimated worldwide prevalence in 2016 of 422 million people, which is expected to rise double to by 2030. Since 1995, there has been an explosion of the introduction of new classes of pharmacological agents having thiazole moieties. However, most of the drugs can cause noncompliance, hypoglycemia, and obesity. Thus, new antidiabetic drugs with thiazole moieties came up with improved compliance and reduced side effects such as pioglitazone (Actos), rosiglitazone (Avandia), netoglitazone, DRF-2189, PHT46, PMT13, DRF-2519. With such a great importance, research in thiazole is part of many academic and industrial laboratories worldwide. CONCLUSION: The present review describes the importance of thiazole nucleus and its derivatives as antidiabetic agents with an emphasis on the past as well as recent developments.

Advancements in Non-steroidal Antiandrogens as Potential Therapeutic Agents for the Treatment of Prostate Cancer.

Prostate cancer (PCa) is a leading cause of death in men worldwide. The main reason for the progression of prostate cancer is identified as over activation of androgen receptor (AR) through androgens. Its development can be diagnosed by monitoring the prostate specific antigen (PSA). Treatment of PCa includes prostatectomy, radiotherapy, and chemotherapy, among them chemotherapy is normally employed in early and advanced prostate cancer. Chemotherapy mainly includes two classes of drugs which are steroidal and non-steroidal antiandrogens. The non-steroidal classes of compounds are preferred over steroidal because they are relatively safe, cost effective and diverse. Non-steroidal drugs are commonly used for the treatment of PCa, however these drugs are associated with serious side effects and acquired resistance. So researchers are working in the direction to develop better analogue which can address the issue related to resistant type of prostate cancer. This review discusses the advancement in the non-steroidal antiandrogens which offers a better potential in the treatment of prostate cancer.