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Background:: Among Nitrogen-containing heterocyclic compounds, pyridazine derivatives serve as a necessary scaffold as they possess various pharmacological activities. Thus, in recent times, the design of novel synthetic schemes and the selection of a new target for the action of pyridazine derivatives have attracted the attention of researchers. Objective:: This study has focused on synthesizing and evaluating the muscle relaxant activity of pyridazine analogs by in-silico screening and rotarod test. Methods: In the present work, pyridazine derivatives were synthesized from substituted pyridine and maleic anhydride yielding intermediates (1a-5a), which on reaction with hydrazine, yielded final pyridazine derivatives (1b-5b). They were then screened for muscle relaxant action by an in-silico docking study against muscarinic acetylcholine receptors with protein data bank ID: 5CXV with the use of Autodock 4.2 and Biovia discovery studio tools. Compounds were further tested for muscle relaxant activity by the rotarod test. Results: Synthesis of the designed compounds was carried out successfully. Obtained result showed that the final compounds (1b-5b) showed 1-3 interactions with acetylcholine muscarinic receptor with -7.2 to -7.9 Kcal/mole affinities. The findings were compared to the typical drug diazepam, which has one interaction with the target and binding energy of -7.7 Kcal/mole. Moreover, the result of the rotarod test showed that substitution by electron-withdrawing groups causes more muscle relaxant activity when compared with the electron releasing groups. Conclusion:: The results of the experimental study showed that pyridazine derivatives could serve as a promising template for the further design and development of muscle relaxant agents.

Background: Even with the massive increase in financial investments in pharmaceutical research over the last decade, the number of new drugs approved has plummeted. As a result, finding new uses for approved pharmaceuticals has become a prominent alternative approach for the pharmaceutical industry. Objective: Drug repurposing or repositioning is a game-changing development in the field of drug research that entails discovering additional uses for previously approved drugs. Methods: In comparison to traditional drug discovery methods, drug repositioning enhances the preclinical steps of creating innovative medications by reducing the cost and time of the process. Drug repositioning depends heavily on available drug-disease data, so the fast development of available data as well as developed computing skills has resulted in the boosting of various new drug repositioning methods. The main goal of this article is to describe these different methods and approaches for drug repurposing. Results: The article describes the basic concept of drug repurposing, its significance in discovering new medications for various disorders, drug repurposing approaches such as computational and experimental approaches, and previous as well as recent applications of drug repurposing in diseases such as cancer, COVID-19, and orphan diseases. Conclusion: The review also addresses obstacles in drug development using drug repurposing strategies, such as a lack of financing and regulatory concerns and concludes with outlining recommendations for overcoming these challenges.

Background: Cancer is an ailment with having a very low survival rate globally. Poor cancer prognosis is primarily caused by the fact that people are found to have the disease when it is already well advanced. The goal of this study is to compile information on new avenues of investigation into biomarkers that may facilitate the routine detection of cancer. Proteomic analysis has recently developed into a crucial technique for cancer biology research, working in tandem with genomic analysis. Mass spectrometry techniques are one of several proteome analysis techniques that allow for the highly precise quantitative and qualitative recognition of hundreds of proteins in small quantities from various biological materials. These findings might soon serve as the foundation for better cancer diagnostic techniques. Methods: An exhaustive literature survey has been conducted using electronic databases such as Google Scholar, Science Direct, and PubMed with keywords of proteomics, applications of proteomics, the technology of proteomics, biomarkers, and patents related to biomarkers. Result: Studies reported till 2021 focusing on cancer proteomics and the related patents have been included in the present review to obtain concrete findings, highlighting the applications of proteomics in cancer. Conclusion: The present review aims to present the overview and insights into cancer proteomics, recent breakthroughs in proteomics techniques, and applications of proteomics with technological advancements, ranging from searching biomarkers to the characterization of molecular pathways, though the entire process is still in its infancy.

The objective of this review is to compile updated scientific information on the conventional and novel approaches to the ocular delivery of medication. Owing to the special features and requirements of a specific site delivery system, there is a need for the refinement of novel drug delivery systems. The conventional ocular dosage forms often possess problems like quick pre-corneal drug excretion because of its nasolacrimal drainage which may lead to tearing turnover and finally result in low ocular bioavailability. The design of novel delivery systems helps in delivering the therapeutic agent very efficiently into the desired areas of the eyes by their unique particle size and also because of their biocompatibility with ocular tissues. In addition, they also offer good contact time, improved drug loading, and releasing properties with less drug loss and low toxicity. All these advantages of a novel delivery system directly cause an improvement in the patient’s satisfaction and the bioavailability of the therapeutic agent. In this review article, information about the different ocular novel drug delivery systems such as nanoparticles, liposomes, niosomes, microneedles, and dendrimers is summarized and discussed. Noteworthy contributions by various researchers in the field of these delivery systems have been also been mentioned. Therefore, this article will be beneficial for future researchers and formulation developers working on the design and development of ocular therapeutic delivery systems.

Background: Significant progress in the field of anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated in order to generate more effective anti-cancer therapeutics. Outline: There have been many attempts to treat cancer, and this review summarizes many bioactive substances obtained from nature that have the ability to fight against different types of malignancies with minimal harm, based on diverse research. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment. Conclusion: Throughout the text, it was concluded that the natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects which are prominent with the conventional drugs used for the treatment of cancer.

Hyperuricemia, also known as gout, has been identified as a well-known metabolic disorder associated with an elevated uric acid level in serum. Gout is commonly associated with various chronic disorders like hypertension, obesity, hyperlipidemia, cardiovascular disorders, and diabetes. Drugs, like nonsteroidal anti-inflammatory medications [NSAIDs] and glucocorticoids, are shown to exhibit serious side effects, when used in this therapy, although they are the first-line of treatment options available to date. Bioactive compounds have been explored for the management of hyperuricemia for their effectiveness and ability to minimize complications. Related research have reported the use of plant-based bioactives on hyperuricemia. The objective of the present review is to highlight the therapeutic effect of the naturally occurring phytochemicals and the pharmacology of the compounds involved in the same. These phytochemicals are categorized into five classes, namely alkaloids, flavonoids, saponins, and phenolic acids, that describe their anti-gout activity. Additionally, the mechanism of action by which these bioactive compounds display the hypouricemic consequences has been divided into three parts, namely, the inhibition of the production of uric acid, lowering of intestinal uric acid secretion, and enhancement of elimination of renal uric acid.

Trapa natans L. is annual aquatic plant generally kwon as Water caltrp, Water chest nut belonging to the Trapaceae or Lytraceae family. Trapa natans L. is use for the treatment of wide no of disease with out proper toxicity study. The present study was designed to evaluate the acute and sub-acute toxicities of Trapa natans L following the OECD guidelines. In acute oral toxicity, the plant extract was administered orally at the doses of 300 mg/kg, 1000 mg/kg, 2000 mg/kg, and 4000 mg/kg. After the dosing, all animals were kept in close observation for 14 days. In the case of the subacute toxicity study, the total number of animals was divided into four groups, each having ten animals, 5 males, and 5 females in each group. Group I was represented as the control, administered orally with aqueous tween 80 solution 2% (v/v), and group II to group IV received plant extract of doses 400, 600, and 1000 mg/kg, respectively, once a day for 28 days. From the acute and subacute toxicity studies, no sign of toxicity was observed. In the sub-acute toxicity study, no major changes were noted on the biochemical parameters and hematological analysis. The experimental results of the toxicity studies suggested that the LD50 values of the Trapa natans L extract were more than 4000mg/kg and thus, the drug was found to be absolutely safe and nontoxic.

Introduction: The purpose of this study was to extract, isolate, and evaluate in vitro the antioxidant and anticancer properties of rutin from Citrus reticulata and Citrus limon. Background: Bioflavonoids are a class of polyphenolic secondary metabolites that give plants their distinctive organoleptic properties. Rutin, also known as rutoside, is a citrus flavonoid that is found in a variety of plants, including citrus fruits, and has a wide range of pharmacological effects. Objective: This investigation's goal was to extract, isolate, and test the antioxidant and anti-cancer properties of rutin in vitro. Method: By incorporating the appropriate solvent system, the Soxhlet apparatus was used to extract C. reticulata (R2) and C. limon (R3) from dried peel powder. Column chromatography was used in the isolation process. Various solvent systems on the basis of their polarity were used to isolate rutin, which further was evaluated for anti-oxidant and anti-cancer action by the use of in vitro tests. Results: Successful extraction and isolation of rutin from two sources were achieved. Additionally, their antioxidant and anticancer activity was also evaluated by in vitro methods. Both isolated rutins (R2 and R3) possessed optimal antioxidants in the range of 31.64 to 76.28 g/ml and anticancer activity with IC50 values of 4 to 7 g/ml, when compared to standard doxorubicin with an IC50 value of 3g/ml. In the comparison of rutin isolated from C. reticulata with rutin isolated from C. limon, rutin isolated from C. reticulata was found to be more abundant and more potent in terms of yield and activity. Conclusion: The study's findings are clear; Citrus reticulata species have a higher flavonoid and phenolic content, and the rutin extracted from them is an effective anti-oxidant and anti-cancer agent against lung cancer. The study can be used as a model for future studies on rutin’s role in cancer.

Background: Modification in sustained release system is a newly developed area that has shown good control over the administration of drug by maintaining systemic concentrations. Objective: The study was conducted to formulate a sustained release tablet of antidiabetic drug, glipizide, with improvement in patient’s compliance. Methods: Sustained release tablet of glipizide was prepared by using different concentration of natural polymers like guar gum, chitosan and xanthan gum as a release modifier by wet granulation method. The tablets had been analyzed by chemical and physical parameters. Drug and polymer interactions had been studied by FT-IR and in vitro drug release had been studied using rotating paddle dissolution apparatus. The release rate had been studied on different models in order to measure their release kinetics. Results: Obtained FT-IR spectra interpreted no interaction of used natural polymers. Over a period of 12 hrs the maximum drug release was 98.66%. Conclusion: The results of the study successfully revealed that the formulated sustained release tablet of glipizide could be formulated by use of natural polymers which could provide maximum drug release and this study could further be explored to formulate other doasage forms by using natural source polymers.

Background: Multiple myeloma (MM) is a hematological malignancy of plasma cells that produce a monoclonal immunoglobulin protein. Despite significant advances in the treatment of MM, currently available therapies are associated with toxicity and resistance. As a result, there is an increasing demand for novel, effective therapeutics. Inhibition of histone deacetylases (HDACs) is emerging as a potential method for treating cancer. HDAC6 is one of 18 different HDAC isoforms that regulate tubulin lysine 40 and function in the microtubule network. HDAC6 participates in tumorigenesis and metastasis through protein ubiquitination, tubulin, and Hsp90. Several studies have found that inhibiting HDAC6 causes AKT and ERK dephosphorylation, which leads to decreased cell proliferation and promotes cancer cell death via the PI3K/AKT and MAPK/ERK signaling pathways. Objective: The objective of this study is to target HDAC6 and identify potent inhibitors for the treatment of multiple myeloma by employing computer-aided drug design. Method: A total of 199,611,439 molecules from five different chemical databases, such as CHEMBL25, ChemSpace, Mcule, MolPort, and ZINC, have been screened against HDAC6 by structure-based virtual screening, followed by filtering for various drug-likeness, ADME, toxicity, consensus molecular docking, and 100 ns MD simulation. Results: Our research work resulted in three molecules that have shown strong binding affinity (CHEMBL2425964 -9.99 kcal/mol, CHEMBL2425966 -9.89 kcal/mol, and CSC067477144 -9.86 kcal/mol) at the active site HDAC6, along with effective ADME properties, low toxicity, and high stability. Inhibiting HDAC6 with these identified molecules will induce AKT and ERK dephosphorylation linked to reduced cell proliferation and promote cancer cell death. Conclusion: CHEMBL2425964, CHEMBL2425966, and CSC067477144 could be effective against multiple myeloma.

Diabetes mellitus (DM) is a metabolic disorder, whose prevalence is predicted to rise shortly. The present review focuses on the various ocular complications associated with DM, and the various ophthalmic formulation approaches developed to treat the same. Diabetic macular edema (DME), diabetic retinopathy, cataracts, and glaucoma are some of the major vision-threatening complications linked to DM. The ocular route of drug delivery has undergone several advancements in recent decades, the introduction of various novel drug delivery systems (DDS), various modifications in the existing formulation approaches, development of custom-designed personalized medications, being some of the major developments introduced in the field of ocular drug delivery. Due to the application of state-of-the-art technologies in the field of innovations related to ocular DDS, patients have been immensely benefited by the current modes of ocular treatment imparting fewer side effects, enhanced penetration, sustained drug effect, and so on. The present review includes and emphasizes the gradual development that has occurred from the conventional ophthalmic dosage forms to the currently reported novel ocular drug delivery approaches along with the related clinical research works.

Computational and experimental techniques are two complimentary approaches that have important roles in drug discovery and development. Earlier time and cost of bringing a new drug in market bears a question as it takes seven to twelve years and $ 1.2 billion are often cited. Furthermore, five out of forty thousand compounds tested in animals reach human testing and only one of five compounds reaching clinical studies is approved. This accounts for a large input in terms of time, money and human and other resources. Therefore, new approaches are needed to facilitate, expedite and streamline drug discovery and development, save time, money and resources. Among many computational tools, molecular docking is one of the important means that can be used in drug discovery. It provides the information regarding the binding affinities between small molecules (ligands) and macromolecular receptor targets (proteins). Various approaches, methodology are cited in various literatures for describing the cost, time effect with success of drug discovery task. In this review, introduction of the available molecular docking methods, with simple methodology of docking and examples of drug design and discovery through computational docking methods is discussed and emphasis is made on various examples of sampling algorithms, scoring functions with their relevant characterstics with summary on type of ligand binding with receptors.

Background: Trapa natans L., is annual aquatic plant generally kwon as Water caltrp, Water chest nut belonging to the Trapaceae or Lytraceae family. Trapa natans L is use for the treatment of wide no of diseases without proper standardization. Objective: To give the right pharmacognostical and photochemical information of the Trapanatan L leaves. In this study pharmacognostical investigation of the fresh leaves and powder drug were done to determine the macroscopical, microscopical, quantitative physicochemical and phytochemical property of the drugs. Method: Macroscopical, quantitative and qualitative microscopy, physicochemical evaluation, extractive value, florescence analysis and phytochemical analysis were done according to the WHO guideline. Result: Macroscopical analysis showed that, leaves are greenish to purplish color, rhomboidal shape; alternate, acute, margin is dentate, pinnate venation. Microscopic evaluation showed that leaf is dorsi ventral in nature, upper layer epidermis cells were covered with cuticle layer. Single layer of barrel shape cell were present bellow the upper epidermis layer. Trichomes are generally multicellular. Anomocytic stomata were observed in upper epidermis. From the experiment it was found that methanolic extract give the highest extractive value. Phytochemical analysis gives the evidence for the presence of carbohydrate, alkaloids, glycoside, steroids, flavonoids, tannin, and triterpenoids. Qualitative phytochemical analysis give the evidence for presence of high amount total phenolic content. Conclusion: Different pharmacognostical parameters assessed in this examination help to detection and standardization of Trapa natans L., leaves.

Background: Flavonoids belong to the chemical class of polyphenols and are in the cate- gory of secondary metabolites imparting a wide protective effect against acute and chronic diseases. Objective: The study aims to investigate and summarize the information of various flavonoids ex-tracted, isolated from various sources, and possess different pharmacological properties by acting on multiple targets. Methods:: This comprehensive review summarizes the research information related to flavonoids and their pharmacological action targets from various sources like PubMed, Google Scholar and Google websites. Result: Extracted information in the paper discusses various therapeutic effects of flavonoids iso-lated from medicinal plant sources, which have the property to inhibit several enzymes, which final-ly results in health benefits like anti-cancer, anti-bacterial, antioxidant, anti-allergic, and anti-viral effects. This study also showed the different solvents and methods involved in the extraction and characterization of the isolated phytochemical constituents. Conclusion: The findings showed the contribution of several flavonoids in the management and in-hibition of various acute and chronic sicknesses by acting on different sites in the body. This study may lead to gaining interest for more research on the bioactives of different medicinal plants for the discovery of new lead compounds or further improvement of the efficacy of the existing compound.

Aim: The aim of this study is to explore the therapeutic potential of S-allylcysteine (SAC) organosulphur compound as a potent immune checkpoint inhibitor PD-L1. Background: Natural compounds have been showing tremendous anticancerous potential via suppressing the expression of genes involved in the development and progression of several carcinomas. This has further motivated us to explore the therapeutic potential of organosulphur compounds as potent immune checkpoint inhibitors. Objective: Our study was designed to elucidate the potential of S-allylcysteine (SAC) as significant PD-L1 (immune checkpoint) inhibitor in human lung cancer A549 cancer cell line by using both the in vitro and in silico approaches. Methods: Anticancerous effect of the SAC on lung cancer cells was determined by using the MTT cell viability. Apoptotic induction was confirmed by Hoechst staining, percent caspase-3 activity as well as gene expression analysis by real time PCR. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Additionally, ligand-target protein interaction was analysed by molecular docking. Result: Cell growth and proliferation was significantly reduced in SAC treated A549 cells in a concentration and time-dependent manner. The effect of SAC on apoptotic induction was analyzed by enhanced nuclear condensation, increased percent caspase-3 activity as well as modulation of apoptotic genes. Furthermore, SAC treatment also resulted in reduced expression of PD-L1 and HIF-1α. Additionally, in silico analysis also supported the in vitro findings by showing efficient docking with PD-L1 immune checkpoint target. Conclusion: Therefore, our results clearly suggested that SAC could serve as a novel chemotherapeutic candidate for the treatment of lung cancer by inhibiting immune checkpoint target PD-L1 in human lung cancer cells. Additionally, our study also explained a novel molecular mechanism of its antitumor activity.

Conjunctivitis, also known as pink eye, is a conjunctival inflammation. It is brought on by bacteria, viruses, toxins, and allergies, including coronaviruses, the most frequent reason being allergic conjunctivitis (AC), which is brought on by exposure to pollutants like pollen, animal hair, or mold. The primary contributor to it is the linkage of immunoglobulin E caused by allergens and receptors on stimulated conjunctival mast cells. As a consequence, mast cells are degranulated, along with the release of histamine, cytokines, chemokines, and lipid mediators. The particular eye tissues impacted and the immune mechanism(s) (both local and systemic) that are involved all play a role in the clinical course, length, intensity, and co-morbidities. It frequently occurs in conjunction with allergic rhinitis, also known as allergic rhino-conjunctivitis and other allergy conditions. Atopic keratoconjunctivitis, giant papillary conjunctivitis, seasonal and perennial conjunctivitis, and vernal keratoconjunctivitis are the different types of allergic conjunctivitis. Ocular allergies are frequently misdiagnosed and undertreated, despite the emergence of innovative therapeutic strategies. This review focuses on several previously published studies to discuss the available therapeutic options for treating allergic conjunctivitis as well as the potential targets for the therapies. The association of conjunctivitis with COVID-19, along with recent patents and research, has also been explored.

This review paper focuses on the different synthetic methodologies that researchers have adopted to synthesize various thiosemicarbazide derivatives with different biological activities of synthesized compounds in the last 20 years. Most of the investigations available in the literature are directed to the biological activities of thiosemicarbazide derivatives with less discussion on its synthetic schemes. This review article presents various reaction scheme, which has been adopted for thiosemicarbazide derivative synthesis along with the reported pharmacological activities of synthesized analogs. The available literature in the article aims to encourage more studies on the synthesis of thiosemicarbazide derivatives, which will help for drug discovery having thiosemicarbazide nucleus.

Background: Anticancer drug development is a tedious process, requiring several in vitro, in vivo, and clinical studies. In order to avoid chemical toxicity in animals during an experiment, it is necessary to envisage toxic doses of screened drugs in vivo at different concentrations. Several in vitro and in vivo studies have been reported to discover the management of cancer. Materials and Methods: This study focused on bringing together a wide range of in vivo and in vitro assay methods developed to evaluate each hallmark feature of cancer. Result: This review provides detailed information on target-based and cell-based screening of new anticancer drugs in the molecular targeting period. This would help in inciting an alteration from the preclinical screening of pragmatic compound-orientated to target-orientated drug selection. Conclusion: Selection methodologies for finding anticancer activity have importance for tumor- specific agents. In this study, advanced rationalization of the cell-based assay is explored along with broad applications of the cell-based methodologies considering other opportunities.

Background: Pulmonary microbial infection is mainly caused by microbes like atypical bacteria, viruses, and fungi, on both the upper and lower respiratory tracts. One of the demands of the present is the use of nanotechnology-based treatments to fight various lung infections. Aim: The main aim of the study is to explore all pulmonary infectious diseases and to compare the advanced and novel treatment approaches with the conventional methods which are available to treat infections. Methods: This work sheds light on pulmonary infectious diseases with their conventional and present treatment approaches along with a focus on the advantageous roles of nano-based formulations. In the literature, it has been reported that the respiratory system is the key target of various infectious diseases which gives rise to various challenges in the treatment of pulmonary infections. Results: The present review article describes the global situation of pulmonary infections and the different strategies which are available for their management, along with their limitations. The article also highlights the advantages and different examples of nanoformulations currently combating the limitations of conventional therapies. Conclusion: The content of the present article further reflects on the summary of recently published research and review works on pulmonary infections, conventional methods of treatment with their limitations, and the role of nano-based approaches to combat the existing infectious diseases which will jointly help the researchers to produce effective drug formulations with desired pharmacological activities.

Background: Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Researchers are continually finding new and more effective medications to battle the diseases. Objective: The objective of this study is to identify the emerging role of Thiosemicarbazide analogs for different types of cancer targets with a glance at different novel synthetic routes reported for their synthesis. Methods: A systematic literature review was conducted from various sources over the last 15 years with the inclusion of published research and review articles that involves the synthesis and use of thiosemicarbazide analogs for different targets of cancer. Data from the literature review for synthesis and anticancer potential for specific targets for cancer studies of thiosemicarbazide analogs are summarized in the paper. Results: There are several emerging studies for new synthetic routes of thiosemicarbazide derivatives with their role in various types of cancers. The main limitation is the lack of clinical trial of the key findings for the emergence of new anticancer medication with thiosemicarbazide moiety. Conclusions: Emerging therapies exist for use of a limited number of medications for the treatment of cancer; results of the ongoing studies will provide more robust evidence in the future.

Objective: The research work unveils the use of nuclear magnetic resonance (NMR) technique for quantitative determination and method validation of obeticholic acid. As standard expository methodology for more up to date medications or formulations may not be available in pharmacopeias, hence it is fundamental need to create novel analytical procedures which should be precise and accurate. Methods: Proton (1H) and carbon (13C) NMR analysis were initially performed to confirm the preliminary authenticity of obeticholic acid API. Method validation was accomplished on the basis of standard guidelines for the parameters, in which tetramethylbenzene as an internal standard and deuterated dimethyl sulfoxide as a diluent were used to assess the obeticholic acid. Results: For the quantification of the drug, the proton nuclear magnetic resonance signals at 0.602 ppm and 6.86 ppm corresponding to the analyte proton of drug and internal standard respectively were used. The curve equation calculated from the regression method, the relative-standard-deviation and correlation-coefficient were found to be 0.743% and 0.9989 respectively, indicating good linearity. Consequently, the quantitative assay of the drug was found to be 99.91% in linearity with limit of detection and quantification values as 0.0773 mg and 0.2344 mg respectively, making successful the study of method validation for obeticholic acid. Conclusion: The advantage of the method was that no reference standard of analyte drug was required for quantification and method validation. The method is non-destructive and can be applied for quantification of drug in commercial pharmaceutical formulation products.

The ocular drug delivery deviates through a number of anatomical and physiological barriers, which have been a bottleneck for the ophthalmologists. The ocular barriers, static and dynamic, decrease the absorption of the therapeutic agents and the entry of the xenobiotics. Thus, a conventional ocular dosage form has various disadvantages of its use in ocular diseases. Hence, an ideal ocular delivery system has always been aimed, where the bioavailability of a drug is maintained for a longer period of time. The present review aims to focus on the drawbacks of the conventional ocular therapy and the advantages of designing novel delivery systems, with their certain specific advantages in ocular pharmacokinetics and the enhancement of bioavailability. These novel approaches emphasize on the benefits of various ocular drug delivery systems, like eye ointments, gels and use of viscosity enhancers, prodrugs, penetration enhancers, microparticles, liposomes, niosomes, ocular inserts, implants, intravitreal injections, nanoparticles, nanosuspension, microemulsion, dendrimers, in situ gels, iontophoresis and periocular injections. The compiled data presented in this review will act as a good information resource and reference point for further researches in the field of ocular drug delivery aiming non-invasive sustained release of drugs in the anterior and posterior segments of the eye.

Background: Atenolol is a commonly used antihypertensive drug of class III BCS category. It suffers from the problem of poor intestinal absorption or permeability thus low bioavailability. The objective of the present study was to enhance the permeability of atenolol by using a suitable technique, which is economical and devoid of using any organic solvent. Methods: The nanocrystal technology by high-pressure homogenization was chosen for this purpose, which is a less expensive and simple method. In this technique, no organic solvent was used. The study was further aimed to characterize prepared nanocrystals in the solid state by Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD) patterns, particle size, zeta potential, %yield and drug permeation study through isolated goat’s intestine. An in-vivo study was carried out to determine the pharmacokinetic property in comparison to pure drug powder using rats as experimental animals. The formulation design was optimized by a 3(2) factorial design. In these designs, two factors namely surfactant amount (X1) and speed of homogenizer (X2) were evaluated on three dependent variables namely particle size (y1), zeta potential (y2) and production yield (y3). Results: PXRD study indicated the presence of high crystal content in the prepared formulation. These nanocrystal formulations were found with a narrow size range from 125 nm to 652 nm and positive zeta potential of 16-18 mV. Optimized formulations showed almost 90% production yield. Permeability study revealed 90.88% drug release for optimized formulation in comparison to the pure drug (31.22%). The FTIR study also exposed that there was no disturbance in the principal peaks of the pure drug atenolol. This confirmed the integrity of the pure drug and its compatibility with the excipients used. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the pure drug. The higher values of the determination coefficient (R2) of all three parameters indicated the goodness of fit of the 3(2) factorial model. The factorial analysis also revealed that speed of homogenizer had a bigger effect on particle size (-0.2812), zeta potential (-0.0004) and production yield (0.0192) whereas amount of surfactant had a lesser effect on production yield (-370.4401), zeta potential (-43.3651) as well as particle size (-6169.2601). Conclusion: It is concluded that the selected method of nanocrystal formation and its further optimization by factorial design was effective to increase the solubility, as well as permeability of atenolol. Further, the systematic approach of factorial design provides rational evaluation and prediction of nanocrystals formulation on the selected limited number of smart experimentation.

Background: Flavonoids are a class of polyphenolic bioactive compounds obtained from plants, which have a wide range of chemical structures and properties. More than 9000 distinct flavonoid molecules have been identified, and have been found to regulate numerous developmental processes and play key biological roles in living organism. Objective: This review aims to highlight the hepatoprotective potentiality of flavonoids and co-relate their pharmacological activity with their chemical structure. Methods: With advancement in the field of research related to phytochemicals, it is evident that flavonoids have versatile health benefits, viz., antioxidant property, free radical scavenging capacity, anticancer activity. The basic structures are C6—C3—C6 rings with various substitution patterns, resulting in a succession of subclass compounds, and the relationships between chemical structures and bioactivity have previously been investigated. Results: The hepatoprotective effects of bioactive flavonoids derived from plants have been widely linked to their antioxidant activity, antiinflammatory activity, effects on sterol regulatory element-binding proteins (SREBP), peroxisome proliferator-activated receptor gamma (PPARγ) receptors, and inflammatory mediator cytokines according to numerous studies. The C2-C3 double bond at the A ring, as well as the hydroxyl groups of C3′or C4′, and the carbonyl group at position C4,have been shown to augment their hepatoprotective activities; however, hydroxymethylation at C3′ and C4′ has been found to diminish the hepatoprotective activity. Conclusion: The impact of flavonoid moieties and the structure-activity relationship of flavonoids related to combating various hepatic disorders have been vividly discussed in this review paper.

Abstract: Cytochrome P450s are a widespread and vast superfamily of hemeprotein monooxygenases that metabolize physiologically essential chemicals necessary for most species' survival, ranging from protists to plants to humans. They catalyze the synthesis of steroid hormones, cholesterol, bile acids, and arachidonate metabolites and the degradation of endogenous compounds, such as steroids, fatty acids, and other catabolizing compounds as an energy source and detoxifying xenobiotics, such as drugs, procarcinogens, and carcinogens. The human CYP17A1 is one of the cytochrome P450 genes located at the 10q chromosome. The gene expression occurs in the adrenals and gonads, with minor amounts in the brain, placenta, and heart. This P450c17 cytochrome gene is a critical steroidogenesis regulator which performs two distinct activities: 17 alpha-hydroxylase activity (converting pregnenolone to 17- hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; these precursors are further processed to provide glucocorticoids and sex hormones) and 17, 20-lyase activity (which converts 17-hydroxypregnenolone to DHEA). Dozens of mutations within CYP17A1 are found to cause 17-alpha-hydroxylase and 17, 20-lyase deficiency. This condition affects the function of certain hormone-producing glands, resulting in high blood pressure levels (hypertension), abnormal sexual development, and other deficiency diseases. This review highlights the changes in CYP17A1 associated with gene-gene interaction, drug-gene interaction, chemical-gene interaction, and its biochemical reactions; they have some insights to correlate with the fascinating functional characteristics of this human steroidogenic gene. The findings of our theoretical results will be helpful to further the design of specific inhibitors of CYP17A1.

Heterocyclic compounds are well known for their different biological activity. The heterocyclic analogs are the building blocks for synthesis of the pharmaceutical active compounds in the organic chemistry. These derivatives show various type of biological activity like anticancer, antiinflammatory, anti-microbial, anti-convulsant, anti-malarial, anti-hypertensive, etc. From the last decade research showed that the quinoline analogs plays a vital role in the development of newer medicinal active compounds for treating various type of disease. Quinoline reported for their antiviral, anticancer, anti-microbial and anti-inflammatory activity. This review will summarize the various synthetic approaches for synthesis of quinoline derivatives and to check their biological activity. Derivatives of quinoline moiety plays very important role in the development of various types of newer drugs and it can be used as lead compounds for future investigation in the field of drug discovery process.

Cancer has been identified as a major cause of mortality around the world fora long. To improve the recovery rates of cancer patients, the development of more effective chemopreventive techniques and treatment methods has become important day by day. Recently, various immune inhibitors, mainly including anti-PD-1 and anti-PDL-1, derived from single cells of monoclonal antibodies, have emerged for a group of cancer patients. Functions of T-cells and tumor-infiltrating lymphocytes (TIL) are suppressed by PD-1 and PDLs, while the function of immunosuppressive regulatory T-cells (Tregs) is increased by the latter. To summarize the role of PD-1 and PDLs immune inhibitors in immuno-oncology (I-O), a huge literature survey has been carried out in Science Direct, Scopus, Pubmed, and various other literature hubs for collection of data. This article is focused on cancer immunotherapy, the mechanism of action of PD-1 and PDLs as immune inhibitors, combinatorial immunotherapy, and various FDA-approved target anticancer drugs working against PD-1 and PDLs, a very novel and important target in the field of personalized anticancer drug delivery. Further, there is a wide scope for cancer researchers in this area to explore in the near future.

Synthesis and investigation of antimicrobial activity of 6 novel 1,8-naphthyridine-3-carboxylic acid derivatives are presented. Among the derivatives, compounds 4a–5b2 showed a broad-spectrum antimicrobial activity against all reference Gram-positive, Gram-negative bacteria and fungi. These compounds exhibited remarkable bactericidal activity against Staphylococcus and Bacillus sps. The tested substances 4a–5b2 were found also found to be active against E. coli, Salmonella and Shigella sps. The chlorine substituted compounds 4a and 5a2 were found to be the most active towards the tested microorganisms. Compounds 4a–5b2 were found to be fungicidal against Candida sp. with a MIC values in the range of 400-2000 μg/ml. Docking studies of these compounds with Salmonella typhi OmpF complexed with ciprofloxacin using PDB- 4KRA revealed that the compounds acted as covalent crosslinker on the DNA gyrase B of the former and intercalate the latter both with higher C score values. Thus, the antibacterial activity against tested strains suggested 1,8-naphthyridine-3-carboxylic acid derivatives warrant further evaluation as potential novel antiinfective agents. The antifungal activity of thse compounds was comparable to that of griseofulvin. The drug-likeness data of synthesized compounds made them promising leads for the future development as antifungal agents.

Although liposomes have proved to be versatile in the field of drug delivery, there are still some issues that need to be addressed mainly problems related to entrapment, penetration, fluidity and stability. Glycerosomes represent a novel drug delivery systems composed of phospholipids, water and glycerol in varying amounts. Glycerosomes are upgraded versions of liposomes meant for topical and transdermal drug delivery. In these preparations, glycerol acts as an edge activator and penetration enhancer. These drug delivery systems manifest improved stability, fluidity, entrapment and penetration in comparison to conventional liposomes. Increasing the concentration of glycerol by 10, 20 or 30 % leads to a drastic increase in glycerosome stability. This article is a detailed review of glycerosomes focusing on methods of preparation, evaluation, applications, advantages and disadvantages based on studies reported so far. In this review article, how the structure of liposomes can be modified by the addition of glycerol and how this modified structure can be used to address the problems related to liposomes is discussed. The influence of increasing glycerol concentration on the nature of glycerosomes that lead to an increase in both entrapment and encapsulation of a drug while causing slower drug release is discussed.

The new era of heterocyclic moieties which are developed in the decades plays a very important role in the treatment of various diseases. Among them are 1,3,4-oxadiazoles, a heterocyclic five-membered ring which plays an vital role in the development of newer medicinal compounds for treating various biological activities, such as proliferation of cells, tuberculosis, allergy, viral diseases, etc. The present review will summarize the various synthetic approaches which will be correlated with the biological activities so that the information in future may be used by many researches to give a path breaking lead in the field of medicinal chemistry.

In the field of molecular modeling, Docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules. In this study a series of synthesized compounds were evaluated for focusing on binding modes, potential interactions and specific binding sites. Chemically compounds bear both the moiety acyl as well as urea and their interaction by using in silico study was investigated with beta tubulin protein that interferes with the tubulin-microtubule equilibrium, crucial for cellular mitosis. In silico studies revealed that synthesized and tested compounds show 1-7 no. of interactions with amino acids of tubulin protein. Docking study was done by using Autodock, it was found that among different synthesized compound some shows the highest and best scoring pose (lowest energy) which was -2.94 Kcal/mole between N (11) and Leucine (113) and -3.09 between N (11) and Alanine (149). Compounds with amino, hydroxy, methyl, methoxy, trimethoxy and dimethoxy substitution in derivatives of acyl urea gave an idea that urea and acyl when used in combination in different synthesized compounds show good antitumor activity.

Objective: Aliskiren hemifumarate is used for the treatment of hypertension. The aim of this research to study the effect on the delivery of drug using natural and synthetic permeation enhancers like limonene, cineol, β-cyclodextrin, and oleic acid by using different polymers. As different penetration acts differently with polymers.Methods: Transdermal patches were prepared by the solvent evaporation technique. The controlled release polymers were used for the preparation of patches. The patches were prepared with different polymers and different plasticizer. The drug and polymer interaction study was performed by Fourier transform infrared spectra. In vitro permeation studies were conducted using pretreated cellophane membrane using franz diffusion cell. Results: The prepared patches were evaluated for in vitro drug release, and the release profile was varied from 52.32% PGH (oleic acid) to 87.63% B (cineol). The permeability coefficient was found in the range of 5.82 to 8.32 cm/h, and corresponding flux was found between 281.61 to 729.08 µg/cm2/h on the prepared patches and statistical analysis performed using t-test (p