Promising Potential of Curcumin and Related Compounds for Antiviral Drug Discovery.

Viruses are acellular, microscopic, and mobile particles containing genetic particles, either DNA/RNA strands as nucleoproteins, responsible for 69,53,743 deaths till the year 2023. Curcumin and related compounds are among the areas of pivotal interest for researchers because of their versatile pharmacological profile. Chemically known as diferuloylmethane, which is a main constituent of turmeric along with demethoxycurcumin and bisdemethoxycurcumin, they have a broad spectrum of antiviral activity against viruses such as human immunodeficiency virus, herpes simplex virus, influenza virus (Avian influenza) and Hepatitis C virus HIV. The possible role of curcumin as an antiviral agent may be attributed to the activation of the 20S proteasome, a cellular machinery responsible for degrading unfolded or misfolded proteins in a ubiquitin-independent manner. It shows suppression of HBV entry at various infection stages by inhibiting cccDNA replication by inhibiting the Wnt/ß-catenin signaling pathway to attenuate IAV-induced myocarditis.

Recent advances in synthetic strategies and SAR of thiazolidin-4-one containing molecules in cancer therapeutics.

Cancer is one of the life-threatening diseases accountable for millions of demises globally. The inadequate effectiveness of the existing chemotherapy and its harmful effects has resulted in the necessity of developing innovative anticancer agents. Thiazolidin-4-one scaffold is among the most important chemical skeletons that illustrate anticancer activity. Thiazolidin-4-one derivatives have been the subject of extensive research and current scientific literature reveals that these compounds have shown significant anticancer activities. This manuscript is an earnest attempt to review novel thiazolidin-4-one derivatives demonstrating considerable potential as anticancer agents along with a brief discussion of medicinal chemistry-related aspects of these compounds and structural activity relationship studies in order to develop possible multi-target enzyme inhibitors. Most recently, various synthetic strategies have been developed by researchers to get various thiazolidin-4-one derivatives. In this review, the authors highlight the various synthetic, green, and nanomaterial-based synthesis routes of thiazolidin-4-ones as well as their role in anticancer activity by inhibition of various enzymes and cell lines. The detailed description of the existing modern standards in the field presented in this article may be interesting and beneficial to the scientists for further exploration of these heterocyclic compounds as possible anticancer agents.

Mechanistic Insights into the Pharmacological Significance of Silymarin.

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of Silybum marianum and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, ß-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.

Recent advances in the vaccine development for the prophylaxis of SARS Covid-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused Coronavirus Disease 2019 (COVID-19) is currently a global pandemic that has wreaked havoc on public health, lives, and the global economy. The present COVID-19 outbreak has put pressure on the scientific community to develop medications and vaccinations to combat COVID-19. However, according to highly optimistic forecasts, we could not have a COVID-19 vaccine until September 2020. This is due to the fact that a successful COVID-19 vaccine will necessitate a careful validation of effectiveness and adverse reactivity given that the target vaccine population includes high-risk people over 60, particularly those with severe co-morbid conditions, frontline healthcare professionals, and those involved in essential industrial sectors. For passive immunization, which is being considered for Covid-19, there are several platforms for vaccine development, each with its own advantages and disadvantages. The COVID-19 pandemic, which is arguably the deadliest in the last 100 years after the Spanish flu, necessitates a swift assessment of the various approaches for their ability to incite protective immunity and safety to prevent unintended immune potentiation, which is crucial to the pathogenesis of this virus. Considering the pandemic's high fatality rate and rapid spread, an efficient vaccination is critical for its management. As a result, academia, industry, and government are collaborating in unprecedented ways to create and test a wide range of vaccinations. In this review, we summarize the Covid-19 vaccine development initiatives, recent trends, difficulties, comparison between traditional vaccines development and Covid-19 vaccines development also listed the approved/authorized, phase-3 and pre-clinical trials Covid-19 vaccines in different countries.

Quinoline-derivatives as privileged scaffolds for medicinal and pharmaceutical chemists: A comprehensive review.

The quinoline scaffolds are privileged for their numerous biological activities in the pharmaceutical field. This moiety constitutes a well-known space in several marketed preparations. The quinoline scaffolds gained attention in modern days being an important chemical moiety in the identification, designing, and synthesis of novel potent derivatives. The current review is developed to shine the light on critical and significant insights on the quinoline derivatives possessing diverse biological activities such as analgesic, anti-inflammatory, antialzheimer, anti-convulsant, anti-oxidant, antimicrobial, anti-cancer activities and so on. A detailed summary of quinoline ring from its origin to the recent advancements regarding its synthesis, green chemistry approaches, patented methods, and its marketed drugs is presented in the review. We attempted to review the literature compiling the critical information that has potential to encourage fellow researchers and scientists for the design and development of quinoline scaffold based active molecules that have improved therapeutic performance along with profound pharmacological properties.

Recent advances in microbial toxin-related strategies to combat cancer.

It is a major concern to treat cancer successfully, due to the distinctive pathophysiology of cancer cells and the gradual manifestation of resistance. Specific action, adverse effects and development of resistance has prompted the urgent requirement of exploring alternative anti-tumour treatment therapies. The naturally derived microbial toxins as a therapy against cancer cells are a promisingly new dimension. Various important microbial toxins such as Diphtheria toxin, Vibrio cholera toxin, Aflatoxin, Patulin, Cryptophycin-55, Chlorella are derived from several bacterial, fungal and algal species. These agents act on different biotargets such as inhibition of protein synthesis, reduction in cell growth, regulation of cell cycle and many cellular processes. Bacterial toxins produce actions primarily by targeting protein moieties and some immunomodulation and few acts through DNA. Fungal toxins appear to have more DNA damaging activity and affect the cell cycle. Algal toxins produce alteration in mitochondrial phosphorylation. In conclusion, microbial toxins and their metabolites appear to have a great potential to provide a promising option for the treatment and management to combat cancer.

Bioactivity and In Silico Studies of Isoquinoline and Related Alkaloids as Promising Antiviral Agents: An Insight.

Viruses are widely recognized as the primary cause of infectious diseases around the world. The ongoing global pandemic due to the emergence of SARS-CoV-2 further added fuel to the fire. The development of therapeutics becomes very difficult as viruses can mutate their genome to become more complex and resistant. Medicinal plants and phytocompounds could be alternative options. Isoquinoline and their related alkaloids are naturally occurring compounds that interfere with multiple pathways including nuclear factor-κB, mitogen-activated protein kinase/extracellular-signal-regulated kinase, and inhibition of Ca2+-mediated fusion. These pathways play a crucial role in viral replication. Thus, the major goal of this study is to comprehend the function of various isoquinoline and related alkaloids in viral infections by examining their potential mechanisms of action, structure-activity relationships (SAR), in silico (particularly for SARS-CoV-2), in vitro and in vivo studies. The current advancements in isoquinoline and related alkaloids as discussed in the present review could facilitate an in-depth understanding of their role in the drug discovery process.

Emerging Role of Flavonoids as the Treatment of Depression.

Depression is one of the most frequently observed psychological disorders, affecting thoughts, feelings, behavior and a sense of well-being in person. As per the WHO, it is projected to be the primitive cause of various other diseases by 2030. Clinically, depression is treated by various types of synthetic medicines that have several limitations such as side-effects, slow-onset action, poor remission and response rates due to complicated pathophysiology involved with depression. Further, clinically, patients cannot be given the treatment unless it affects adversely the job or family. In addition, synthetic drugs are usually single targeted drugs. Unlike synthetic medicaments, there are many plants that have flavonoids and producing action on multiple molecular targets and exhibit anti-depressant action by affecting multiple neuronal transmissions or pathways such as noradrenergic, serotonergic, GABAnergic and dopaminergic; inhibition of monoamine oxidase and tropomyosin receptor kinase B; simultaneous increase in nerve growth and brain-derived neurotrophic factors. Such herbal drugs with flavonoids are likely to be useful in patients with sub-clinical depression. This review is an attempt to analyze pre-clinical studies, structural activity relationship and characteristics of reported isolated flavonoids, which may be considered for clinical trials for the development of therapeutically useful antidepressant.

Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer.

Cancer, a fatal disease, is also one of the main causes of death worldwide. Despite various developments to prevent and treat cancer, the side effects of anticancer drugs remain a major concern. Ascorbic acid is an essential vitamin required by our bodies for normal physiological function and also has antioxidant and anticancer activity. Although the body cannot synthesize ascorbic acid, it is abundant in nature through foods and other natural sources and also exists as a nutritional food supplement. In anticancer drug development, ascorbic acid has played an important role by inhibiting the development of cancer through various mechanisms, including scavenging reactive oxygen species (ROS), selectively producing ROS and encouraging their cytotoxicity against tumour cells, preventing glucose metabolism, serving as an epigenetic regulator, and regulating the expression of HIF in tumour cells. Several ascorbic acid analogues have been produced to date for their anticancer and antioxidant activity. The current review summarizes the mechanisms behind ascorbic acid's antitumor activity, presents a compilation of its derivatives and their biological activity as anticancer agents, and discusses delivery systems such as liposomes, nanoparticles against cancer, and patents on ascorbic acid as anticancer agents.

Thiazole-containing compounds as therapeutic targets for cancer therapy.

In the last few decades, considerable progress has been made in anticancer agents development, and several new anticancer agents of natural and synthetic origin have been produced. Among heterocyclic compounds, thiazole, a 5-membered unique heterocyclic motif containing sulphur and nitrogen atoms, serves as an essential core scaffold in several medicinally important compounds. Thiazole nucleus is a fundamental part of some clinically applied anticancer drugs, such as dasatinib, dabrafenib, ixabepilone, patellamide A, and epothilone. Recently, thiazole-containing compounds have been successfully developed as possible inhibitors of several biological targets, including enzyme-linked receptor(s) located on the cell membrane, (i.e., polymerase inhibitors) and the cell cycle (i.e., microtubular inhibitors). Moreover, these compounds have been proven to exhibit high effectiveness, potent anticancer activity, and less toxicity. This review presents current research on thiazoles and elucidates their biological importance in anticancer drug discovery. The findings may aid researchers in the rational design of more potent and bio-target specific anticancer drug molecules.

Synthesis, Characterization and Antimicrobial Evaluation of Lipid Based Norfloxacin Prodrug.

BACKGROUND: Fluoroquinolones, the synthetic antibacterial agents are being successfully utilized against bacterial infections, since the time immemorial. Despite of enormous useful features, these drugs are associated with some limitations also. Large number of efforts has been made by various scientists to improve pharmacokinetic properties of these drugs and hence, to overcome the limitations associated with them. OBJECTIVES: The aim of this paper is to introduce a novel scheme for synthesis of prodrug with improved pharmacokinetic properties i.e., lipophilicity and consequently, modified bioavailability of norfloxacin. METHODS: Fatty acid hydrazide of selected fatty acid was synthesized followed by preparation of 5-formyl salicylamide. N-Mannich base of norfloxacin was synthesized by reacting norfloxacin with 5-formyl salicylamide. The prodrug was obtained by covalently coupling this N-Mannich base of norfloxacin with fatty acid hydrazide. The synthesized lipid based prodrug was evaluated for partition coefficient by shake flask method and screened for antimicrobial activity against selected strains. Drug content determination and in vitro dissolution studies utilizing HPLC were also carried out. RESULTS: The synthesized prodrug was found to exhibit improved partition coefficient (1.15) when compared with parent drug, norfloxacin (0.46). The results of antimicrobial evaluation indicate promising antibacterial and antifungal activity. CONCLUSION: The synthesized prodrug proved to be a good antimicrobial substance due to improved lipophilicity and would be expected to be used as a suitable candidate for exploration of possible utilities in treatment of bacterial infections in forthcoming time.

Synthesis and characterization of N-Mannich based prodrugs of ciprofloxacin and norfloxacin: In vitro anthelmintic and cytotoxic evaluation.

Prodrugs, the inert derivatives of existing drugs have successfully contributed to the modification of their physicochemical properties. The improved antimicrobial potential due to enhanced lipophilicity of some of the synthesized prodrugs of antibacterial agents by various schemes has already been reported. In the current study, synthesis, characterization, and biological evaluation of some more lipid based prodrugs/compounds of ciprofloxacin and norfloxacin has been carried out. The synthesized prodrugs/compounds have been screened for anthelmintic activity using Indian earthworms and cytotoxic activity against human lung cancer cell lines A-549 employing sulforhodamine B (SRB) assay method. The prodrugs FQF1, 6b, 6c, and 6k were found to possess promising anthelmintic activity due to improved partition coefficient. Growth of selected cells lines was found to decrease with increase in concentration of prodrugs as compared to parent drug. Prodrug, 6k having GI50 value 28.8, has been proved to be the most active among all the synthesized prodrugs. Results of present investigation reveal that some of the synthesized prodrugs/compounds were found to possess promising biological activity.

Benzothiazole Derivatives as Potential Anti-Infective Agents.

BACKGROUND: Severity of microbial infections and escalating resistance towards antibiotics has created a deep necessity for discovery of novel anti-infective agents. Heterocyclic chemistry of benzothiazole has become one of the most prolific areas in the field of drug discovery and development that has attracted great attention in recent time due to its increasing importance in the field of pharmaceuticals. METHOD: The importance of benzothiazole and derivatives as potential antimicrobial agents has been well established and a large number of papers have been published in this regard. RESULT: The present communication is an earnest attempt to review the chemistry, synthetic aspects including click chemistry and antimicrobial activities of benzothiazole derivatives reported in recent scientific literature. CONCLUSION: The scientific information of this manuscript may be worthwhile in encouraging the prospective researchers working on this heterocyclic scaffold.

Insight into Prodrugs of Quinolones and Fluoroquinolones.

Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy.

Prodrugs of Antiinfective Agents: A Review.

Prodrugs are the pharmacologically inactive derivatives of active drugs typically intended to optimize the exposure of active drug at target site, through manipulation of its physicochemical, biopharmaceutical or pharmacokinetic properties. This approach has a number of advantages over conventional drug administration. Antiinfective agents are associated with number of limitations, responsible for their reduced bioavailability. Various antiinfective prodrugs have been synthesized with reduced side effects and improved pharmacological properties. The present paper illustrates different vistas of prodrug approach of antiinfective agents describing brief classification, synthetic approaches, pharmacological aspects and recent patents. It is a very productive area of research and its prologue in human therapy has given triumphant outcomes in improving the clinical and therapeutic effectiveness of drugs.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Imidazole Derivatives as Potential Therapeutic Agents.

BACKGROUND: The imidazole nucleus is inimitable and ubiquitous and it is very well known to play an important role in living organisms. Imidazole derivatives are under intensive scientific exploration due to their diverse and significant pharmacological activities. METHODS: The present paper is an attempt to discuss chemistry, synthetic aspects including click chemistry procedures of imidazoles through systematic literature survey. RESULTS: Biological activity profiles of the imidazole derivatives reported in recent scientific literature from 2000 to 2015 have been discussed in detail. It has been found that imidazole derivatives depict appreciable antiinfective activity potential. CONCLUSION: It is anticipated that the information compiled in this paper will be useful and motivating to prospective researchers working on this heterocylic scaffold.

Simple and efficient way to detect small polymorphic bands in plants.

There are many ways to detect polymorphism. In this study we use the microsatellite markers to detect the polymorphism for the salt tolerance. This method has been successfully conducted in Oryza sativa and Brassica juncea. The results are reproducible. In contrast to previous methods, our method is simple and quite accurate for detecting the polymorphic bands. In this study instead of using agarose gel and ethidium bromide staining, we used non-denaturing polyacrylamide gel and a low-cost improved method for silver staining when we compare it to 11 other methods for their ability to detect simple sequence repeat polymorphisms as small as 50 bp in denaturing polyacrylamide gels. All methods detected the same alleles and banding pattern. However, important differences in sensitivity, contrast, time consumption and background were observed.

Cabazitaxel: a novel drug for hormone-refractory prostate cancer.

Cabazitaxel has recently been approved by FDA for the treatment of docetaxel resistant hormone-refractory prostate cancer. It has been developed by Sanofi-Aventis under the trade name of Jevtana. It is given in combination with prednisone/prednisolone and has passed the clinical trial over well-known drug mitoxantrone. This drug is a microtubule depolymerization inhibitor, which can penetrate blood brain barrier (BBB). The FDA granted fast track designation to this drug in November 2009 and thereafter, new drug application submission was done in March 2010. Priority review to this drug was granted in April 2010 and finally in July 2010 it was approved by FDA. It is available in the form of injection in the dose of 60 mg/1.5 mL, which should be diluted prior to its use by the diluents supplied along with the injection. It is a second-line drug and has proven to be effective in patients experiencing docetaxel based treatment failure.

Medicinal significance of benzothiazole scaffold: an insight view.

Heterocycles bearing nitrogen, sulphur and thiazole moieties constitute the core structure of a number of biologically interesting compounds. Benzothiazole, a group of xenobiotic compounds containing a benzene ring fused with a thiazole ring, are used worldwide for a variety of therapeutic applications. Benzothiazole and their heterocyclic derivatives represent an important class of compounds possessing a wide spectrum of biological activities. The myriad spectrum of medicinal properties associated with benzothiazole related drugs has encouraged the medicinal chemists to synthesize a large number of novel therapeutic agents. Several analogues containing benzothiazole ring system exhibit significant antitumour, antimicrobial, antidiabetic, anti-inflammatory, anticonvulsant, antiviral, antioxidant, antitubercular, antimalarial, antiasthmatic, anthelmintic, photosensitizing, diuretic, analgesic and other activities. This article is an attempt to present the research work reported in recent scientific literature on different pharmacological activities of benzothiazole compounds.