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.

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.

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.

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.

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, challenges and updates on the development of therapeutics for malaria.

Malaria has developed as a serious worldwide health issue as a result of the introduction of resistant Plasmodium species strains. Because of the common chemo resistance to most of the existing drugs on the market, it poses a severe health problem and significant obstacles in drug research. Malaria treatment has evolved during the last two decades in response to Plasmodium falciparum drug sensitivity and a return of the disease in tropical areas. Plasmodium falciparum is now highly resistant to the majority of antimalarial drugs. The parasite resistance drew focus to developing novel antimalarials to combat parasite resistance. The requirement for many novel antimalarial drugs in the future year necessitates adopting various drug development methodologies. Different innovative strategies for discovering antimalarial drugs are now being examined here. This review is primarily concerned with the description of newly synthesized antimalarial compounds, i.e. Tafenoquine, Cipargamin, Ferroquine, Artefenomel, DSM265, MMV390048 designed to improve the activity of pure antimalarial enantiomers. In this review, we selected the representative malarial drugs in clinical trials, classified them with detailed targets according to their action, discussed the relationship within the human trials, and generated a summative discussion with prospective expectations.

Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity.

Two novel series of N(4)-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N(1)-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enylidene)semicarbazide and N(4)-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N(1)-(3,7-dimethylocta-3,6-dienylidene)-semicarbazide were synthesized to meet structural prerequisite indispensable for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. The rotorod test was conducted to evaluate neurotoxicity. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The outcome of the present investigations proved that the four binding sites pharmacophore model is vital for anticonvulsant activity. The efforts were also made to establish structure-activity relationships among test compounds.

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.

Synthesis and biological evaluation of novel benzothiazole clubbed fluoroquinolone derivatives.

In the present investigation, synthesis and anti-bacterial, analgesic and anthelmintic evaluation of a novel series of fluoroquinolone derivatives clubbed with benzothiazole moeity has been described. The synthesized compounds were characterised by spectral analysis (IR and (1)H NMR). Preliminary results indicated that the most of the synthesized compounds demonstrated good activities against gram negative and gram positive bacterial strains. Compounds 5a, 5b, 5f and 5k demonstrated potent anti-bacterial activities. Compound 5a exhibited most potent anti-bacterial activity with MIC values of 04, 03, 08 and 15 µg/ mL against B. subtilis, S. aureus, E. coli and P. aeruginosa. Analogs 5a, 5c, 5g and 5h showed promising anthelmintic activity against Eisemia foetida in a low concentration as compared to standard drug piperazine citrate with mean paralysis time ranging 22.60 ± 2.46 to 31.60 ± 3.07 min. All synthesized compounds depicted good in vivo analgesic activity with compound 5a exhibiting the most potent activity of 55.19% inhibition of writhing in comparison to the standard drug.

Synthesis and antiepileptic activity of some novel semicarbazones containing 1,3,4-thiadiazole and quinazoline ring.

The incomplete seizure control with frequent adverse effects of current anticonvulsant drugs and the importance of semicarbazones, quinazolines and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore prompted us to carry out synthesis of three novel series of semicarbazones containing 1,3,4-thiadiazole and quinazoline ring. The chemical structures of these compounds were elucidated by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The rotorod test was conducted to evaluate neurotoxicity. The majority of the compounds were found active in the biological screening. The outcome of the present investigations proved that the four binding sites pharmacophore model is decisive for antiepileptic activity. An attempt has also been performed to establish structure-activity relationships among synthesized compounds.

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.

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.

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.

2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors.

The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.

Pharmacological significance of triazole scaffold.

The triazole nucleus is one of the most important and well known heterocycles which is a common and integral feature of a variety of natural products and medicinal agents. Triazole nucleus is present as a core structural component in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, antihypertensive, antimalarial, local anaesthetic, antianxiety, antidepressant, antihistaminic, antioxidant, antitubercular, anti-Parkinson's, antidiabetic, antiobesity and immunomodulatory agents, etc. The broad and potent activity of triazole and their derivatives has established them as pharmacologically significant scaffolds. The basic heterocyclic rings present in the various medicinal agents are 1,2,3-triazole and 1,2,4-triazole. A large volume of research has been carried out on triazole and their derivatives, which has proved the pharmacological importance of this heterocyclic nucleus. The present paper is an attempt to review the pharmacological activities reported for triazole derivatives in the current literature with an update of recent research findings on this nuclei.

Synthesis of some novel 2,5-disubstituted thiazolidinones from a long chain fatty acid as possible anti-inflammatory, analgesic and hydrogen peroxide scavenging agents.

Some new decanoic acid [2,5-disubstituted-4-oxo-thiazolidin-3-yl]amides (6a-j) have been synthesised by the condensation of decanoic acid hydrazide with various aromatic aldehydes to yield the Schiff's bases. Cyclocondensation of the Schiff's bases with thioglycollic acid afforded 4-thiazolidinone derivatives. The structures of the newly synthesised compounds were confirmed by analytical and spectral methods. The anti-inflammatory, analgesic and antioxidant activity of the title compounds were evaluated. Compound 6j exhibited 44.84 % inhibition of inflammation and was the most potent anti-inflammatory agent of the series whereas compound 6f demonstrated the most potent analgesic activity (69.82% inhibition of writhing) followed by compounds 6e and 6g. All the synthesised compounds exhibited a potent antioxidant activity.

Thiazolidin-4-one and hydrazone derivatives of capric acid as possible anti-inflammatory, analgesic and hydrogen peroxide-scavenging agents.

Starting from capric acid, hydrazone and thiazolidin-4-one derivatives have been synthesized in the present investigation. Decanoic acid hydrazide was reacted appropriately to yield hydrazones, which were then cyclized to yield the corresponding thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by analytical and spectral methods. Anti-inflammatory, analgesic, and hydrogen peroxide-scavenging activity of the title compounds were evaluated. Among synthesized compounds, 2-hydroxyphenyl thiazolidinone with 44.90% inhibition of inflammation was the most potent anti-inflammatory agent. Similarly, 4-methoxybenzylidine hydrazide with 64.90% inhibition of writhing was observed to be the most potent analgesic agent of the synthesized compounds. All the synthesized compounds exhibited potent hydrogen peroxide-scavenging activity.

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.

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.

Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects.

In the current practices of anti-infective therapy, ciprofloxacin is a very popular fluoroquinolone having a broad spectrum of activity and diverse therapeutic prospects. The reasons for its wide use include multiresistant pathogens susceptible only to ciprofloxacin. The available clinical evidence suggests the potentially enhanced efficacy of this drug in the treatment of various community acquired and nosocomial infections, e.g. respiratory tract, urinary tract, and skin infections and sexually transmitted diseases. As compared to other agents of its class, the pharmacokinetic profile of ciprofloxacin demonstrates equivalent or greater bioavailability, higher plasma concentrations, and increased tissue penetration, as reflected in the greater volume of distribution. Various molecular modifications of this drug have been made to further improve its characteristics. Several methods of analytical determination of ciprofloxacin and its metabolites in biological fluids employing various techniques have been reported. The present article is focused on the synthetic development, pharmacotherapeutic, and analytical evaluation vistas of ciprofloxacin.