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Rhodanine or 2-Thioxothiazolidin-4-one is a privileged heterocyclic compound offering a wide opportunity for structural modification, lead development, and modification. It is one of the highly decorated scaffolds in the drug discovery process. Rhodanine derivatives possess a plethora of biological activities due to their ability to interact with a diverse range of protein targets, which provide tremendous opportunities to discover new drugs with different modes of action. The most common strategy for developing novel rhodanine derivatives is the introduction of structurally diverse substituents at the C-5 or N-3, or both positions. Since the inception of Epralestat into the market in 1992, the exploration of rhodanine-3-acetic acids has led to the development of novel leads against different biological targets such as MRSA, HHV-6, Mycobacterial tuberculosis, dengue, etc. In the current pandemic era, some rhodanine compounds have been explored against SARS-CoV-2. In recent years, rhodanine and its derivatives have witnessed significant progress in developing new drug leads as potential antimicrobial and antiviral agents. Different synthetic methodologies and recent developments in the medicinal chemistry of rhodanine derivatives, including biological activities, their mechanistic aspects, structure-activity relationships, and in silico findings, have been compiled in the present review. This article will benefit the scientific community and offer perspectives on how these scaffolds as privileged structures might be exploited in the future for rational design and discovery of rhodanine-based bio-active molecules.

Heterocyclic compounds offer an enormous area for new lead molecules for drug discovery. Till today, efforts are being continuously made to find appropriate treatment for the management of the deadly disease of cancer. Amongst the large number of heterocycles that are found in nature, heterocycles having oxygen obtained noteworthy attention due to their distinctive and pharmacological activities.‘Pyran’ is one of the most significant non-aromatic, sixmembered ring composed of one oxygen atom and five carbon atoms. It is considered a privileged structure since pyran and its related derivatives exhibit a wide spectrum of biological activities. Pyran derivatives are found to have excellent anti-cancer properties against various types of cancer. The present review focussed on the current advances in different types of pyran-based derivatives as anti-cancer agents. Various in vitro (cell based testing), in vivo (animal based testing) models as well as molecular docking along with results are also covered. A subsection describing briefly natural pyran containing anticancer compounds is also incorporated in the review.

Abstract: Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of the investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan, and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors.

During the global pandemic, e-learning became even more popular and used by many educational institutions worldwide to facilitate the students' learning process. Students can easily get the related materials and resources from e-learning. This research intends to examine the level of students' satisfaction with e-learning and their learning experiences during the global pandemic. The quantitative research method was carried out using a questionnaire survey and online research. 150 students from different institutions in India and Malaysia have participated in the survey. The survey was carried out through Google Form and the data were exported to be analyzed using SPSS. The results showed that most of the students were satisfied with e-learning and how e-learning helped them in their studies. The results of this study indicated that convenience flexibility was significantly related to students’ learning experiences.

Background: The platinum (II) complexes as anticancer agents have been well explored for the development of novel analogs. Yet, none of them achieved clinical importance in oncology. At present, anticancer compounds containing platinum (II) complexes have been employed in the treatment of colorectal, lung, and genitourinary tumors. Among the platinum-based anticancer drugs, Cisplatin (cis-diamine dichloroplatinum (II), cis-[Pt(NH3)2Cl2]) is one of the most potent components of cancer chemotherapy. The nephrotoxicity, neurotoxicity and ototoxicity, and platinum compounds associated resistant cancer are some major disadvantages. Objective: With the rapidly growing interest in platinum (II) complexes in tumor chemotherapy, researchers have synthesized many new platinum analogs as anticancer agents that show better cytotoxicity, and less off-target effects with less cellular resistance. This follows the introduction of oxaliplatin, water-soluble carboplatin, multinuclear platinum and newly synthesized complexes, etc. Method: This review emphasizes recent advancements in drug design and development, the mechanism of platinum (II) complexes, their stereochemistry, current updates, and biomedical applications of platinum-based anticancer agents. Conclusion: In the last few decades, the popularity of platinum complexes as potent anti-cancer agents has risen as scientists have synthesized many new platinum complexes that exhibit better cytotoxicity coupled with less off-target effects.

Background: Having various limitations in conventional drug delivery system, it is important to focus on the target-specific drug delivery system where we can deliver the drug without any degradation. Among various challenges that are thrown to a formulation scientist, delivering the drug to its right site, in its right dose, is also an important aim. A focused drug transport aims to extend, localize, target and have a safe drug interaction with the diseased tissue. Objective: The aim of targeted drug delivery is to make the required amount of the drug available at its desired site of action. Drug targeting can be accomplished in a number of ways that include enzyme mediation, pH-dependent release, use of special vehicles, receptor targeting, among other mechanisms. Intelligently designed targeted drug delivery systems also offer the advantages of a low dose of the drug along with reduced side effects which ultimately improves patient compliance. Incidences of dose dumping and dosage form failure are negligible. A focused drug transport aims to have a safe drug interaction with the diseased tissue. Conclusion: This review focuses on the available targeting techniques from experiment to perfection for delivery to the colon, brain, and other sites of interest. Overall, the article should make an excellent read for the researchers in this area. Newer drug targets may be identified and exploited for successful drug targeting.

Abstract:: Schiff base or imine or azomethine is one of the most important organic compounds that has been reported to play a significant role in various biological processes. The group is a part of natural or non-natural compounds and is involved as important precursors as diversified agents and as intermediates for the synthesis of biologically active agents. The review outlines the detailed design strategy, synthesis and structure-activity relationship studies of different Schiff bases for various biological activities. We have tried to outline the key points of various researchers with respect to biological activities. The results of different studies demonstrate Schiff bases as a linker in many synthetic compounds displaying a broad range of activities. We believe that the present review will provide comprehensive knowledge about medicinal importance of Schiff bases and serve as important literature in designing the synthesis of novel molecules containing Schiff base as pharmacophore or biologically active moiety.

The present work reports the synthesis and screening of fifteen 2,5-disubstituted-4- thiazolidinones with different substitutions at imino and varied arylidene groups. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti- inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group thereby ensuring possible freedom from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals as depicted by DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five and the toxicity behavior of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

During the global pandemic, e-learning became even more popular and used by many educational institutions worldwide to facilitate the students' learning process. Students can easily get the related materials and resources from e-learning. This research intends to examine the level of students’ satisfaction with e-learning and their learning experiences during the global pandemic. The quantitative research method was carried out using a questionnaire survey and online research. A total of 150 students from different institutions in India and Malaysia have participated in the survey. The survey was carried out through Google Form and the data were exported to be analyzed using SPSS. The results showed that most of the students were satisfied with e-learning and how it helped them in their studies. The results of this study indicated that convenience flexibility was significantly related to students’ learning experiences.

ICP-OES is a powerful, versatile, and advanced analytical technique with excellent detection properties. Due to its extraordinary features, it has been widely employed for the analysis of a wide variety of chemical elements in the past few years with great success. It offers the least detection time, lower detection limits, broader linear dynamic range, and greater matrix tolerability as well as negligible chemical interferences. Beyond this, it can handle multiple varieties of samples including aqueous, inorganic, organic liquids, and solids as well. It comprises complex instrumental makeup which enables it to detect up to 2 to 70 elements simultaneously with great accuracy. Recent reports evidenced that this hyphenated technique has been employed in several analytical determinations including food analysis, agricultural investigations, geological studies, drug/metabolite analysis, and environmental and forensic sciences. In the present compilation, a detailed description of the fundamental principles of ICP-OES has been provided along with its various sophisticated functional components. Also, the reported applications of this technique in different fields have been discussed highlighting the basic experimental setups and outcomes by presenting the data as tables. This summarization may be helpful to analysts to get insights into the working as well as performance characteristics of this technique.

A sizeable proportion of currently marketed drugs come from heterocycles. The heterocyclic moiety 5-pyrazolone is well known five-membered ring containing nitrogen. Derivatives of this wonder nucleus have exhibited activities as diverse as antimicrobial, anti-inflammatory, analgesic, antidepressant, anticonvulsant, antidiabetic, antihyperlipidemic, antiviral, antitubercular, antioxidant, anticancer and antiviral, including action against severe acute respiratory syndrome (SARS) or 3C protease inhibitor. A number of drugs based on this motif have already made it to the market. Standard texts and literature on medicinal chemistry cite different approaches for the synthesis of 5- pyrazolones. The present review provides an insight view to 5-pyrazolone synthesis, their biological profile and structure-activity relationship studies.

The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities, including inflammatory action. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure. Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant, etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have a significant anti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate it as an anti-inflammatory agent. In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a threestep reaction. The compounds were subjected to spectral analysis by Infrared, Mass, and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized derivatives were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Compounds PT-1, PT-3, PT-4, and PT-8 exhibited significant anti-inflammatory activity at 3rd hour, being 50.7%, 54.3%, 52.3%, and 57%, respectively, closer to that of the standard drug indomethacin (61.9%). From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed a docking score of -6.5 kJ/mol, compound PT-1 exhibited the highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 had a docking score of 9.4 kJ/mol for COX-2. It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors was very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized.

The sodium dependent SLC13 family transporters comprise of the five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them the three NaDC1, NaDC3 and NaCT are sodium dependent transporters such as di-carboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, the information to the structures is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these receptors and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of the citrate present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporter are required for the development of citrate inhibitors. In this review the structure, function, and regulation of the NaCT receptors are discussed. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT receptors are succinctly summarized.

Neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington's Disease (HD), are characterized by progressive neuronal dysfunction and death. Recent studies have established detrimental modifications in the structure and function of brain proteins, which stimulate their aggregation, misfolding and deposition in and around the neurons an important hallmark of neurodegenerative diseases. Post-Translational Modification (PTM) of proteins, including phosphorylation, acetylation, glycosylation, palmitoylation, SUMOylation, and ubiquitination, are important regulators of protein characteristics, including stability, intracellular distribution, activity, interactions, aggregation and clearance. Despite clear evidence that altered protein modifications emerging from impromptu chemical modifications to side chains of amino acid are associated with neurodegeneration, the underlying mechanisms that promote aberrant PTM remain poorly understood. Therefore, elucidating PTM of specific disease-associated proteins can prove to be a significant step in evaluating the functional alteration of proteins and their association with neurodegeneration. This review describes how aberrant PTM of various proteins is linked with the neurodegenerative disease pathogenesis, as well as molecular strategies targeting these modifications for treating such diseases, which are yet incurable.

Background: Measuring medicinal compounds to evaluate their quality and efficacy has been recognized as a useful approach in treatment. Rhubarb anthraquinones compounds (mainly including aloe-emodin, rhein, emodin, chrysophanol, and physcion) are the main effective components in purgating drug. In the current Chinese Pharmacopoeia, the total anthraquinones content is designated as its quantitative quality and control index, while the content of each compound has not been specified. Methods: On the basis of forty rhubarb samples, the correlation models between the near infrared spectra and UPLC analysis data were constructed using support vector machine (SVM) and partial least square (PLS) methods, according to the Kennard and Stone algorithm for dividing the calibration/ prediction datasets. Good models mean they have high correlation coefficients (R2) and low root mean squared error of prediction (RMSEP) values. Results: The models constructed by SVM have much better performance than those by PLS methods. The SVM models have high R2 of 0.8951, 0.9738, 0.9849, 0.9779, 0.9411, and 0.9862 that correspond to aloe-emodin, rhein, emodin, chrysophanol, physcion and total anthraquinones contents, respectively. The corresponding RMSEPs are 0.3592, 0.4182, 0.4508, 0.7121, 0.8365, and 1.7910, respectively. 75% of the predicted results have relative differences being lower than 10%. As for rhein and total anthraquinones, all of the predicted results have relative differences being lower than 10%. Conclusion: The non-linear models constructed by SVM showed good performances with predicted values close to the experimental values. This can perform the rapid determination of the main medicinal ingredients in rhubarb medicinal materials.

Heterocyclic are a class of compounds that are intricately entwined into life processes. Almost more than 90% of marketed drugs carry heterocycles. Synthetic chemistry, in turn, allocates a cornucopia of heterocycles. Among the heterocycles, indole, a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring with numerous pharmacophores that generate a library of various lead molecules. Due to its profound pharmacological profile, indole got wider attention around the globe to explore it fully in the interest of mankind. The current review covers recent advancements on indole in the design of various anti-cancer agents acting by targeting various enzymes or receptors, including (HDACs), sirtuins, PIM kinases, DNA topoisomerases, and σ receptors.

The airline industry plays a vital role in stimulating social, and economic development. Thus, Garuda Indonesia implements various strategies and promotions to face the fast-changing pricing condition and the fierce competitive condition in the local and international markets. This study aims to systematically describe the characteristics of the factors improving Garuda Indonesia Airline’s profitability for its further opportunity exploration and to establish some limitations it is currently facing. To understand how they fully work and to provide more suggestions for the improvements of its overall operational activities, some data will be collected and analyzed.

Refractory epilepsy is a type of epilepsy involving seizures uncontrolled by first or second- line anticonvulsant drugs at a regular therapeutic dose. Despite considerable growth in epileptic pharmacotherapy, one-third of the patients are resistant to current therapies. In this, the mechanisms responsible for resistant epilepsy are either increased expulsion of antiepileptic drugs (AEDs) by multidrug resistance (MDR) transporters from the epileptogenic tissue or reduced sensitivity of drug in epileptogenic brain tissue. The difficulty to treat refractory epilepsy is because of drug resistance due to cellular drug efflux, use of drug monotherapy, and subtherapeutic dose administration. Increased expression of Pgp is also responsible for resistance epilepsy or refractory epilepsy. Increased glutamate expression via inhibition of cyclooxygenase-II (COX-II) enzyme also upregulate P-glycoprotein (Pgp) expression and augment instance of recurrent seizures. Peripheral and central inhibition of Pgp is a powerful tool to control this drug resistant epilepsy. Drug resistance primarily involves multidrug resistance (MDR1) gene responsible for encoding P-glycoprotein (Pg- P1 or MDR1). Currently, there is no drug under clinical practice which inhibits MDR1. The present review cites some drugs like Calcium Channel Blockers (CCBs), COX-II inhibitors, and glutamate receptors antagonists that inhibit P-gp. The exploitation of these targets may emerge as a beneficial approach for patients with drug-resistant epilepsy. The present review further highlights the mechanistic role of Pgp in drug-resistant epilepsy, glutamate role in drug efflux, and management approach.

Background: Anxiety and oxidative stress are the common disorders prevailing in the modern age. Many new pyrazoline derivatives have been synthesized and patented, but there is still continuous research in progress to explore antidepressant and antioxidant potential of pyrazoline scaffold. Objective: The present work was carried out to synthesize, characterize and evaluate the pharmacological potential of 1,3,5-Pyrazoline derivatives. Methods: Ten new 1,3,5-Pyrazoline derivatives were synthesized and characterized by IR, 1HNMR and mass spectral techniques. The synthesized pyrazoline derivatives were investigated for their in vivo antidepressant activity by Tail Suspension Test (TST) and in vitro antioxidant activity by FRAP and DPPH assay methods. The docking studies and in silico ADME and toxicity characteristics were also evaluated. Results: Among the synthesized analogues, IVh showed the highest antidepressant activity with a significant reduction in the duration of immobility. The compound IVh emerged as the most potent antioxidant compound due to the presence of an electron releasing hydroxyl group. Docking studies of most potent compounds revealed good interaction points with the MAO-A enzyme. The compounds were found to obey Lipinski’s Rule of Five and displayed the least in silico toxicity profile. Conclusion: The synthesized compounds were found to possess great potential in decreasing the duration of immobility in Swiss albino mice and scavenging free radicals. These compounds may serve as new leads for further drug exploration.

Background: An upsurge in the number of antibiotic-resistant microbial infections has warranted the discovery and development of new antibiotics. This is a matter of great concern for effective therapy for a search of novel antimicrobial agents. Literature has a number of reports of involvement of oxidative stress due to an imbalance between the generation and neutralization of free radicals in many diseases. Heterocyclic compounds have been involved in the treatment of various disorders. Benzothiazole is one such heterocyclic nucleus having benzene ring merged with the thiazole ring. Among the various substitutions possible in this nucleus, substitutions at position-2 have already been reported with potential bioactivities. Thus, different substituted compounds have been synthesized which could serve as antimicrobials and antioxidants. Methods: Benzothiazole derivatives (B1-B7) were synthesized by two-step reactions and the structures were confirmed through infrared, mass and NMR spectroscopy. The compounds were evaluated for in vitro antioxidant and antimicrobial activities using standard methods. Results: The results of antibacterial and antifungal activity showed that compound B4 exhibited maximum activity against all the tested strains of microorganisms with the zone of inhibition 17.1-18.5 mm and MIC value 1.1-1.5 μg/mL. Compound B5 exhibited potent antioxidant activity. Conclusion: The compounds substituted with halogen on the aryl ring showed increased antimicrobial activity as seen in the case of compound B4 (6-fluoro). The compounds substituted with a hydroxyl group (B5) exhibited good antioxidant activity.

A series of eleven thiazolidine-2, 4-dione (TZD) derivatives, were synthesized and characterized by FT-IR, 1 H NMR and mass spectral analysis. All the synthesized TZD derivatives were screened for their in vitro and in vivo anti-diabetic and antioxidant, activities and cytotoxicity. In vivo antihyperglycemic effect was assessed by measuring plasma glucose (PG) levels in alloxan-induced type II diabetic rat models. The compound 4h exhibited better blood glucose lowering activity than the standard drug rosiglitazone. The synthesized TZD derivatives were evaluated for hepatotoxicity and pancreatic tissue studies. Antioxidant activity was evaluated by DPPH method and H2 O2 method. Compounds 4a and 4b exhibited potent antioxidant activity. Among the tested compounds for cytotoxicity using MTT assay method, compound 4i exhibited better viability and cytotoxicity activity. Thiazolidinedione derivatives were evaluated for their affinity towards target PPARg, using rosiglitazone as the reference compound molecular docking visualization through FlexX docking program. From selected anti-diabetic targets, the proposed derivatives exhibited better interaction with PPARγ receptor, where rosiglitazone showed docking score of -19.891 kJ/ mol, compound 4h exhibited highest docking score of -31.6068 kJ/mol. The study showed that all the studied compounds were showing higher docking score when compared to control drug rosiglitazone and it could be a remarkable starting point to evaluate structure activity relationships to develop new lead molecules with potential anti-diabetic activities.

Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

Epidermal growth factor receptor (EGFR) is a vital intermediate in cell signaling pathway including cell proliferation, angiogenesis, apoptosis, and metastatic spread and also having four divergent members with similar structural features, such as EGFR (HER1/ErbB1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). Despite this, clinically exploited inhibitors of EGFR (including erlotinib, lapatinib, gefitinib, selumetinib, etc.) are not specific thus provoking unenviable adverse effects. Some of the paramount obstacles to generate and develop new lead molecules of EGFR inhibitors are drug resistance, mutation, and also selectivity which inspire medicinal chemists to generate novel chemotypes. The discovery of therapeutic agents that inhibit the precise stage in tumorous cells such as EGFR is one of the chief successful targets in many cancer therapies, including lung and breast cancers. This review aims to compile the various recent progressions (2016-2021) in the discovery and development of diverse epidermal growth factor receptor (EGFR) inhibitors belonging to distinct structural classes like pyrazoline, pyrazole, imidazole, pyrimidine, coumarin, benzothiazole, etc. We have summarized preclinical and clinical data, structure-activity relationships (SAR) containing mechanistic and in silico studies to provide proposals for the design and invention of new EGFR inhibitors with therapeutic significance. The detailed progress of the work in the field will provide inexorable scope for the development of novel drug candidates with greater selectivity and efficacy.

Background: Racecadotril and Ofloxacin (RACIGYL- O) drug combination are used for the treatment of diarrhea. The drugs have been estimated individually in formulations but no method has been developed for simultaneous estimation of these two drugs as combination. Objective: To develop and validate a high performance liquid chromatography method for the simultaneous estimation of Racecadotril and Ofloxacin in tablet dosage form. Method: A WATERS C18 column (250 x 4.6mm, 5 μm) with mobile phase consisting of acetonitrile, methanol and water 40:40:20v/v (pH adjusted to 2.7 of water with ortho phosphoric acid). The flow rate was 1.0mL/min and effluents were monitored at 210nm. Results: The retention time of RAC and OFL was 4.666 min and 2.551 min respectively. The developed method was validated according to ICH guidelines with respect to specificity, linearity, accuracy, precision, robustness, Limit of Detection (LOD) and Limit of Quantification (LOQ). Conclusion: The method show good reproducibility and recovery with %RSD less than 2. So the proposed method was found to be simple, rapid, precise and accurate and useful for the determination of RAC and OFL in bulk and pharmaceutical dosage forms. Keywords: RP-HPLC, Racecadotril, Ofloxacin, ICH guidelines.

Objective: The aim of the study is to develop and validate a high-performance liquid chromatographic method for the simultaneous determination of clotrimazole, miconazole nitrate, and tinidazole tablet dosage forms. Materials and Methods: A Waters C18 column (50 mm×4.6 mm, 5 μm) with mobile phase consisting of acetonitrile, methanol, and water 55:25:20 (v/v) (pH 2.5 adjusting with 0.5% orthophosphoric acid) was used. The flow rate was 1.0 ml/min, and effluents were monitored at 210 nm. Results: The retention time of miconazole nitrate, tinidazole, and clotrimazole tablets was found to be 2.9 min, 3.5 min, and 4.7 min, respectively. The method was validated according to the ICH guidelines for specificity, limit of detection, limit of quantification, precision, accuracy, linearity, ruggedness, and robustness. Conclusion: The method shows good reproducibility and recovery with % relative standard deviation

Background: Multiple antibiotic resistant bacteria represent a challenge in the treatment of infections. It is imperative, therefore, that new substances with antimicrobial properties should be searched to fight these microorganisms. Objective: A series of 5-benzylidene-2, 4-dioxothiazolidin-3-yl benzoic acid derivatives were synthesized and evaluated their antimicrobial potential. The compounds were synthesized by both conventional and microwave synthesizers. Methods: In this study, a series of 5-benzylidene-2, 4-dioxothiazolidin-3-yl benzoic acid derivatives were synthesized by Knoevenagel condensation of 2, 4-thiazolidinedione with substituted aryl aldehydes followed by substitution of 3-amino group with p-chlorobenzoic acid. All the synthesized compounds were characterized by spectral (FT-IR, mass and 1HNMR) and elemental analysis. The compounds were evaluated for their in-vitro antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria and a fungal strain by agar well diffusion assay method and solid dilution method. Results: The compounds exhibited appreciable antimicrobial activity. Compound 4-(5-(2- chlorobenzylidene)-2, 4-dioxothiazolidin-3-yl)benzoic acid (3f) expressed potent antimicrobial activities against all of the microbial strains examined in this study with MIC values ranging between 0.6-0.8 µg/mL and diameter of the zone of inhibition between 17.2-19.5 mm at the concentration of 200 µg/mL. Conclusion: There was a marked decrease in the reaction time, under mild conditions through microwave synthesis wherein it presented a green approach towards syntheses of the thiazolidinedione derivatives. All compounds exhibited mild to moderate antimicrobial activity. The results of tested bioactive assay showed that the nature of the substituent on the phenyl ring significantly influenced the antimicrobial activity. Among the chloro, bromo and methoxy substituted derivatives, chloro derivative possessed the highest activity followed by bromo and then methoxy. The position of the substituents on the arylidene nucleus also affected the activity and it was found that generally ortho-substituted derivatives showed better antimicrobial activity than others.

Background: Communicable diseases have always been a threat to mankind since times immemorial. Leishmaniasis, an infectious disease caused by protozoan of various species of leishmania, is a major health problem spreading across 98 countries and about 350 million people stand the risk of this infection worldwide. Medical research has struggled a lot to combat this disease. Objective: Among the various approaches available for treatment of Leishmaniasis, many are costly so there is a need to develop effective but economical and easily available antileishmanial agents. Methods: Natural products are important source of various new medicaments and their derivatives can be used for synthetic modification and bioactivity optimization. Therefore, in order to fulfil the need for novel, economical, more effective and safer chemotherapeutic agents, scientists have explored Mother Nature in detail. Results: A number of plant species possess inhibitory activity against certain types of parasites such as Leishmania major, Leishmania amazonensis, Leishmania aethiopica, Leishmania braziliensis, Leishmania mexicana, Leishmania infantum, Leishmania chagasi and Leishmania donovani. Moreover natural products are economical, safer, more effective and without considerable side effects. Conclusion: The present review highlights the leishmanicidal activity of various natural products with an insight in to their possible mechanism.

In order to optimize drug action, new drug formulations have been developed based upon the prodrug approach. This study was inspired by the increasing interest in the field of macromolecular prodrugs and Piroxicam maleate was used as a model drug. A total of five prodrugs were synthesized using beta cyclodextrin, chitosan, pectin, egg albumin, bovine serum albumin. The synthesized conjugates were characterized on the basis of UV, IR and NMR techniques. In-vitro hydrolysis studies were carried out at pH 1.2, pH 7.4, pH 9.0 and in 80% human plasma followed by in-vivo evaluation of analgesic, anti-inflammatory and anti-ulcerogenic potential. The extent of hydrolysis was found to be proportional to increase in pH. Beta cyclodextrin conjugate was found to possess significant analgesic activity whereas chitosan conjugate was found to be the best anti-inflammatory. Pectin conjugate provided maximum protection against ulcers.

The present research was aimed at the synthesis and screening of 35 novel 2-(substituted phenyl imino)-5-benzylidene-4-thiazolidinones having different substitutions at imino phenyl and arylidene groups. The title compounds were synthesized by Knoevenagel condensation at the 5th position of the 4-thiazolidinone ring, in the presence of sodium acetate. The structures were assigned on the basis of spectral data. The compounds were screened for in vivo anti-inflammatory, antinociceptive and in vitro free-radical scavenging activities. The compounds exhibited significant activities when compared with standard drugs. The distinctive property of the derivatives was that none of them had an acidic group, like conventional NSAIDs, but exhibited significant in vivo activity in acute inflammation models. Further, the active compounds of each series were docked against cyclooxygeanase (COX)-2 enzyme using Glide module of Maestro 11.1 program. It was evident from the docking results that 3-chlorophenylimino and 2-chloro moiety on 5-benzylidene nucleus of the 4-thiazolidinone derivative (30) could easily fit into the COX-2-binding pocket, considered as critical interaction for COX-2 inhibition. Interestingly, some of the compounds exhibited the potential of becoming dual action or even triple action drug candidates, which could target degenerative disorders associated with excessive free-radical generation.

The mitogen activated protein kinase (MAPK) belongs to group of kinase that links the extracellular stimuli to intracellular response. The MAPK signalling pathway (RAS-RAF-MEK-ERK) involved in different pathological conditions like cancer, caused due to genetic or any other factor such as physical or environmental. Many studies have been conducted on the pathological view of MAPK cascade and its associated element like RAS, RAF, MEK, ERK or its isoforms, and still the research is going on particularly with respect to its activation, regulation and inhibition. The MAPK signalling pathway has become the area of research to identify new target for the management of cancer. A number of heterocyclics are key to fight with the cancer associated with these enzymes thus give some hope in the management of cancer by inhibiting MAPK cascade. In the present article, we have focussed on MAPK signalling pathway and role of different heterocyclic scaffolds bearing nitrogen, sulphur and oxygen and about their potential to block MAPK signalling pathway. The heterocyclics are gaining importance due to high potency and selectivity with less off-target effects against different targets involved in the MAPK signalling pathway. We have tried to cover recent advancements in the MAPK signalling pathway inhibitors with an aim to get better understanding of the mechanism of action of the compounds. Several compounds in the preclinical and clinical studies have been thoroughly dealt with. In addition to the synthetic compounds, a significant number of natural products containing heterocyclic moieties as MAPK signalling pathway inhibitors have been put together. The structure activity relationship along with docking studies have been discussed to apprehend the mechanistic studies of various compounds that will ultimately help to design and develop more MAPK signalling pathway inhibitors.

Background: Prostate cancer is considered the second most diagnosed cancer, and one of the most common causes of death from cancer in men. Apalutamide is an effective, safe, and well-tolerated agent used for the treatment of men with non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) and metastatic Hormone-Naive Prostate Cancer (mHNPC). Androgen receptor signaling is a leading factor that drives these prostate tumors. USFDA has approved apalutamide on 14 February 2018 as an agent that targets androgen receptor signaling through inhibition causing significant improvement in metastasis-free survival in patients with prostate cancer. Objective: In this review, various aspects related to apalutamide have been summarized which involve the mechanism of action, chemistry, synthesis, pharmacokinetics, pharmacodynamics, adverse reactions, and safety parameters. Methods: The literature was thoroughly searched in the relevant databases to identify studies published in this field during recent years. Special attention has been given to apalutamide clinical trials phases and its promising future as one of the first-line agents for the treatment of patients with advanced prostate cancer. Results: Ongoing trials are progressing for apalutamide monotherapy and also for its combinations in other disease settings. The expected results of such trials will shape the future scenario of prostate cancer therapy. Conclusion: This review article has highlighted different aspects of Apalutamide like its mechanism of action, adverse effects, pharmacokinetics, pharmacodynamics, clinical trials among others. The contents of this article should make an excellent read for prospective researchers in this field.

Various traditional herbal plants have been associated with unique pharmacological actions. Natural parts as well as processed plant parts are known to possess gastro-protective and gastro- mucosal healing property. Motive of this review analysis is to explain the gastro-protective and gastro-mucosal healing property of different herbal plants and their constituents indigenous to various regions of the globe and elucidate mechanisms of the healing by their metabolic extracts. Moreover, an attempt shall be made to explicate the possible molecular pharmacological targets responsible for healing gastric ulcer activity. A thorough survey of literature has been carried out from various scientific resources and using keywords like peptic ulcer mechanism, gastro-protective agents, gastro-mucosal healing property, natural and processed herbal drugs preventing peptic ulcers. This article will present a running commentary on the prospects and potential of herbal plants exhibiting gastroprotective activity and gastro-mucosal healing property.

Background: Lurbinectedin was approved on June 15, 2020 by the Food and Drug Administration with the brand name ZEPZELCA as the first systematic approved therapy for patients having Small Cell Lung Cancer (SCLC). Objectives: In this review, an attempt is made to summarize different aspects of Lurbinectedin, including the pathophysiology, chemistry, chemical synthesis, mechanism of action, adverse reactions, and pharmacokinetics. Special attention is given to various reported clinical trials of lurbinectedin. Methods: A comprehensive literature search was conducted in the relevant databases like ScienceDirect, PubMed, ResearchGate and Google Scholar to identify studies. After a thorough study of these reports, significant findings/data were collected and compiled under suitable headings. Important findings related to clinical trials have been tabulated. Conclusion: Lurbinectedin is known to act by inhibiting the active transcription of encoding genes, thereby suppressing tumor-related macrophages with an impact on tumour atmosphere. Lurbinectedin has emerged as a potential drug candidate for the treatment of Small-Cell Lung Cancer (SCLC).

The ambit of nanotechnology to bring about carriers that are target-specific in order to achieve desired therapeutic response is gaining significance in medical and pharmaceutical field. The development of polymer lipid hybrid nanoparticles for codelivery of hydrophilic and lipophilic drugs is a new revolution in the field and has helped to overcome many of the limitations associated with cancer therapy. The advent of hybrid nanoparticles is expected to be advantageous over chemotherapy or radiation therapy as cancer chemotherapeutics. The increased interest in such nanoparticles can be attributed to their target-specific action, ease of controlling release, and ability to provide controlled release. Further, pegylated hybrid nanoparticles can avoid opsonization and thus help to increase the circulation half-life of the drugs. This chapter will focus on the advantages, disadvantages, methods of preparation, applications in the diagnosis and treatment of cancer, and future prospects of polymer lipid hybrid nanoparticles.

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task in both the past and present. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is discovering novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents.

Background: Cancer can be considered as a genetic as well as a metabolic disorder. The current cancer treatment scenario looks like aggravating tumor cell metabolism, causing the disease to progress even with greater intensity. The cancer therapy is restricted to the limitations of poor patient compliance due to toxicities to normal tissues and multi-drug resistance development. There is an emerging need for cancer therapy to be more focused towards better understanding of genetic, epigenetic and transcriptional changes resulting in cancer progression and their relationship with treatment sensitivity. Objective: The 4-thiazolidinone nucleus possesses marked anticancer potential towards different biotargets, thus targeting different cancer types like breast, prostate, lung, colorectal and colon cancers, renal cell adenocarcinomas and gliomas. Therefore, conjugating the 4-thiazolidinone scaffold with other promising moieties or directing the therapy towards targeted drug delivery systems like the use of nanocarrier systems, can provide the gateway for optimizing the anticancer efficiency and minimizing the adverse effects and drug resistance development, thus providing stimulus for personalized pharmacotherapy. Methods: An exhaustive literature survey has been done to give an insight into the anticancer potential of the 4- thiazolidinone nucleus either alone or in conjugation with other active moieties, with the mechanisms involved in preventing proliferation and metastasis of cancer covering a vast range of publications of repute. Conclusion: This review aims to summarise the work reported on anticancer activity of 4-thiazolidinone derivatives covering various cancer biomarkers and pathways involved, citing the data from the year 2005 till now, which may be beneficial to the researchers for future development of more efficient 4-thiazolidinone derivatives.

Background:The complication of Alzheimer’s disease (AD) has made the development of its therapeutic a challenging task. Even after decades of research, we have achieved no more than a few years of symptomatic relief. The inability to diagnose the disease early is the major hurdle behind its treatment. Several studies have aimed to identify potential biomarkers that can be detected in body fluids (CSF, blood, urine, etc.) or assessed by neuroimaging (i.e., PET and MRI). However, the clinical implementation of these biomarkers is incomplete as they cannot be validated.Method:This study aimed to overcome the limitation of using artificial intelligence along with technical tools that have been extensively investigated for AD diagnosis. For developing a promising artificial intelligence strategy that can diagnose AD early, it is critical to supervise neuropsychological outcomes and imaging-based readouts with a proper clinical review.Conclusion:Profound knowledge, a large data pool, and detailed investigations are required for the successful implementation of this tool. This review will enlighten various aspects of early diagnosis of AD using artificial intelligence.

Coronaviruses have led to severe emergencies in the world since the outbreak of SARS CoV in 2002, followed by MERS CoV in 2012. SARS CoV-2, the novel pandemic caused by coronaviruses that began in December 2019 in China has led to a total of 24,066,076 confirmed cases and a death toll of 823,572 as reported by World Health Organisation on 26 August 2020, spreading to 213 countries and territories. However, there are still no vaccines or medications available till date against SARS coronaviruses which is an urgent requirement to control the current pandemic like situations. Since many decades, heterocyclic scaffolds have been explored exhaustively for their anticancer, antimalarial, anti-inflammatory, antitubercular, antimicrobial, antidiabetic, antiviral and many more treatment capabilities. Therefore, through this review, we have tried to emphasize on the anticipated role of heterocyclic scaffolds in the design and discovery of the much-awaited anti-SARS CoV-2 therapy, by exploring the research articles depicting different heterocyclic moieties as targeting SARS, MERS and SARS CoV-2 coronaviruses. The heterocyclic motifs mentioned in the review can serve as crucial resources for the development of SARS coronaviruses treatment strategies.

Twenty different batches of gels containing metaxalone and diclofenac potassium were prepared for topical application. These drugs act synergistically in the management of pain and inflammation. Gels were prepared by varying the type of gelling agent (ten batches each of hydroxyl propyl methyl cellulose and carbopol 934). The prepared gels were characterized and evaluated. Batch F7 emerged as the best batch on the basis of favourable pH, high drug content, homogeneity and drug release. HPLC (High-performance liquid chromatography) method validation of gel formulation was also carried out and the developed and validated method was found to be robust and accurate.