Tuberculosis (TB), caused by mycobacterial strains, remains a global threat, especially due to multidrugresistant forms. Enoyl acyl carrier protein reductase (InhA) mutations contribute to resistance in 20-25% of clinical isolates, highlighting the need for novel inhibitors. The present study involves in silico analysis of eighty-one naphthalene-based hydrazone derivatives against InhA (PDB ID: 2X22). Compounds 78 and 79 showed strong binding affinities (-11.61 to -11.69 kcal/mol) as compared to the reference drug Isoniazid (binding energy = -5.28 kcal/mol) and favorable pharmacokinetic profiles. Compound 78 has shown high thermodynamic stability throughout 100 ns MD simulation without any major fluctuation, while DFT analysis confirmed the electronic stability of compounds 78 and 79 (Delta E = 0.159 eV and 0.149 eV, respectively). Therefore, compounds 78 and 79 may act as lead molecules in the development of potent antitubercular agents for the successful clinical management of resistant TB.

A series of quinoline derivatives (4a-k) have been synthesized and tested to assess ADMET properties, docking behaviour, and antibacterial potential. A series of various quinoline derivatives have been synthesized by a simple and efficient three-component reaction using anilines, aromatic aldehydes and ethyl acetoacetate with acetonitrile as a solvent. The characterization of the synthesized compounds have been done by IR and NMR spectroscopy. Compound 4d shows the highest binding affinity of-8.4 kcal/mol. Strong interactions that involved key amino acids have also been observed. ADMET analysis reveals outstanding intestinal absorption and CNS permeability. The antibacterial activity of synthesized quinoline derivatives have been evaluated using the agar diffusion method against two Gram-positive and two Gram-negative bacteria, with ciprofloxacin as the standard. Compounds 4c, 4d, and 4j show broad-spectrum activity, with 4c demonstrating the most consistent and potent inhibition, surpassing ciprofloxacin against B. subtilis and E. coli, making it a promising lead for further development. Two-way ANOVA analysis shows no statistically significant difference in antibacterial activity among the tested compounds (p = 0.891) or bacterial strains (p = 0.431), indicating a uniform response. However, Tukey's HSD test confirmed that no compound could significantly outperform ciprofloxacin.

Background:: Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moi-ety as celecoxib, and lonazolac as COX-II inhibitors. Aims:: We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately. Methods:: Purified and characterized pyrazoles have been analyzed for in-vivo analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies. Results:: The ADME profile of synthesized compounds was found to be satisfactory. Conclusion:: The synthesized compounds can serve as lead for further drug designing.

BACKGROUND:Inflammatory, immune, and neurodegenerative diseases constitute a category of persistent and debilitating conditions affecting millions worldwide, with inter-twined pathophysiological pathways. Recent research has spotlighted naturally occurring compounds like naringenin for potential therapeutic applications across multiple ailments. OBJECTIVE:This review offers an encompassing exploration of naringenin's anti-inflamma-tory, immune-protective, and neuroprotective mechanisms, elucidating its pharmacological targets, signal transduction pathways, safety profile, and insights from clinical investigations. METHODS:Data for this review were amassed through the scrutiny of various published studies via search engines such as PubMed and Google Scholar. Content from reputable publishers including Bentham Science, Taylor and Francis, Nature, PLOS ONE, among others, was referenced. RESULTS:Naringenin exhibits substantial anti-inflammatory effects by restraining the NF-κB signaling pathway. It activates Nrf2, renowned for its anti-inflammatory properties, inducing the release of hemeoxynase-1 by macrophages. Furthermore, naringenin treatment downregulates the expression of Th1 cytokines and inflammatory mediators. It also impedes xanthine oxidase, counteracts reactive oxygen species (ROS), scavenges superoxide radicals, mitigates the accessibility of oxygen-induced K+ erythrocytes, and reduces lipid peroxidation. Naringenin's antioxidant prowess holds promise for addressing neurological conditions. CONCLUSION:Extensive research has been undertaken to establish the anti-inflammatory, immunomodulatory, and neuroprotective attributes of naringenin across various medical domains, lending credence to its pharmacological utility. The principal obstacle to naringenin's adoption as a therapeutic agent remains the dearth of in vivo data. Efforts should focus on rendering naringenin delivery patient-friendly, economically viable, and technologically advanced.

A series of oxadiazole-based five-membered heterocyclic derivatives was designed and synthesized with the intent of exclusive cyclo-oxygenase-2 (COX-2) inhibition to acquire anti-inflammatory activity without the presence of gastric toxicity. Oxadiazole-based novel analogs were designed by using bioisosteric substitutions and were screened against the macromolecular target by using docking-based virtual screening to identify their potential inhibitors. These selective COX-2 inhibitors were further evaluated for their stability within the binding cavity of macromolecular complex by performing molecular dynamic simulation for 100 ns. Selected compounds were synthesized by using Naphthalene-2-yl-acetic acid as a starting material based on the fundamental structure of naphthalene. The naphthalene ring and methylene bridge of naphthalene-2-yl-acetic acid were retained in the rational molecular design by replacing the carboxyl group with biologically significant groups like 1,3,4-oxadiazoles, with the goal of obtaining a novel, superior, and relatively safe anti-inflammatory molecule with better efficacy and optimized pharmacokinetics. Anti-inflammatory as well as analgesic properties of the compounds were evaluated experimentally for their pharmacological efficiency.

Antimicrobial resistance (AMR) is a worldwide concern among infectious diseases due to increased mortality, morbidity and treatment cost. According to WHO 2019 report, among the 32 antibiotics in the clinical trials, only six were classified as innovative and containing novel moiety. The remaining antibiotics from this list contain previously known moiety (WHO AMR 2019). Therefore, the development of novel antibiotics to control resistance problems is crucial. Benzothiazole derivatives are of great interest due to their wide range of biological activities and medicinal applications. Reported data indicated that benzothiazole derivatives displayed antibacterial activity by inhibiting the dihydroorotase, DNA gyrase, uridine diphosphate-n-acetyl enol pyruvyl glucosamine reductase (MurB), peptide deformylase, aldose reductase, casdihydrofolate reductase, enoyl acyl carrier protein reductase, dialkylglycine decarboxylase, dehydrosqualene synthase, dihydropteroate synthase and tyrosine kinase. The present review analyzed the synthesis, structure-activity relationship (SAR) and mechanism of action studies of benzothiazole derivatives as antibacterial agents reported by various research groups in the last five years (2018–2022). Different patents on the antimicrobial activity of benzothiazole derivatives have also been summarized. The finding of the present review will be beneficial for the researchers in the development of novel antibacterial molecules based on benzothiazole moiety.

Due to the emergence of drug-resistant microbial strains, different research groups are continuously developing novel drug molecules against already exploited and unexploited targets. 1,3,4-Oxadiazole derivatives exhibited noteworthy antimicrobial activities. The presence of 1,3,4-oxadiazole moiety in antimicrobial agents can modify their polarity and flexibility, which significantly improves biological activities due to various bonded and non-bonded interactions viz. hydrogen bond, steric, electrostatic, and hydrophobic with target sites. The present review elaborates the therapeutic targets and mode of interaction of 1,3,4-oxadiazoles as antimicrobial agents. 1,3,4-oxadiazole derivatives target enoyl reductase (InhA), 14α-demethylase in the mycobacterial cell; GlcN-6-P synthase, thymidylate synthase, peptide deformylase, RNA polymerase, dehydrosqualene synthase in bacterial strains; ergosterol biosynthesis pathway, P450-14α demethylase, protein-N-myristoyltransferase in fungal strains; FtsZ protein, interfere with purine and functional protein synthesis in plant bacteria. The present review also summarizes the effect of different moieties and functional groups on the antimicrobial activity of 1,3,4-oxadiazole derivatives.

The current study is done for formulating and characterizing self-emulsifying drug delivery system (SEDDS).In the current research it has been shown that the SEDDS is a tedious pharmaceutical technology which has the potential for the improvement in biopharmaceutics properties like absorption, metabolism, distribution and excretion of Cyclosporin A also opens new window for developing the procedures to enhance the solubility of low water solubilised drugs.The stability in gastrointestinal drug as well as rate of absorption of drug in SEDDS can be increased by this approach.3 types of methods were used for the formulation of Self emulsifying drug delivery system (SEDDS) containing cyclosporine: Cold homogenisation method, Hot Homogenisation method and method of injection with the use of emulsifying agent and stabilising agent.The optimisation of formulation variables were done with the use of 33 factorial design.The analysation of 3 independent formulation variables were done at the time of study which includes the concentration of surfactant (A), concentration of stabiliser (B) and lipid concentration (C).The droplet size (X) and polydispersity index (Y) were the investigated dependent variables .The complete experiment includes 27 designed points.The pattern of release of optimized formulation was almost similar to the release pattern of marketed formulation.Less nephrotoxicity and less inflammation is observed in SEDDS containing Cyclosporin A when compared with available marketed product.Hence, SEDDS containing Cyclosporin A is a system which is very important for the enhancement of solubility of drugs which have very less solubility in water.

The discovery of new drug molecules in the current era has come with incidences of low water solubility.The less solubility of drug in water decreases oral bioavailability of the drug molecules.According to biopharmaceutics classification system, the drugs are categorized as per their solubility and membrane permeability.BCS class II shows high membrane penetration with low water solubility.The low water solubility of drugs presents a problem in their release when given orally.Formulation of SLN (solid lipid nanoparticle) is one of the leading approach to improve the poor water solubility of the drug.Its ability to encapsulate the drug in lipid matrix offers a precursor in advanced level of drug targeting.Griseofulvin is widely used anti-fungal drug of BCS class II.In this study, the griseofulvin containing solid lipid nanoparticles were formulated by three methods.The method optimization was done on entrapment efficiency, size of particles and yield.The optimization of variables was done using response surface method using 33 factorial designs.In this technique, three factors were investigated, at two different levels, and formulation trials were carried out over 27 possible combinations.The surfactant concentration (A), drug: lipid ratio (B), stabilizer concentration (C) were considered independent variables whereas the size of particles (X) and polydispersity index (Y) were considered as dependent variables.The in-vitro release investigation of drug containing solid lipid nanoparticles was compared with pure drug suspension where the solid lipid nanoparticles showed extended release of drug up to 24 hours with 89.47 %.

PHF14 (PHD finger protein 14) is associated with Plant Homeodomain (PHD) Finger Protein family. This chromatin-binding protein interacts with histones. PHF14 overexpression has gained attention due to compelling evidence of its involvement in cell proliferation of various cell lines. PHF14 plays a critical function in the induction of pulmonary fibrosis, and actively participate in cell mitosis which makes it a probable target in the treatment of lung fibrosis and can also be utilized as a biomarker in evaluation and management of non small cell lung cancer. A model of PHF14 protein was prepared by homology modelling and was verified by Ramachandran plot. This model of PHF14 protein was acknowledged by Protein Model Data Base (PMDB) and has been assigned PMDB ID: PM0084114. The DrugBank database was used to obtain ligands, to dock against PHF14 by applying PatchDock technique. The structure of the selected ligand (DB08438) was then modified by means of ACD/ChemSketch 8.0 to secure 22 new in silico ligands, which were subjected to the docking procedure. The docking results identify ligand 31 to possess a high binding affinity with the target protein. The in silico docking results suggests that ligands 31, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 26, 29, 30, 31, 32, and 33 have a high preference for binding with PHF14 and these compounds should be thoroughly probed so as to develop potential chemical entities for the suppression of malignant transformation and tumorigenicity of non small cell lung cancer.

1,3,4-oxadiazole is a five membered heterocyclic aromatic moiety, present in a number of antimicrobial agents. 2,5- disubstituted 1,3,4-oxadiazole derivatives have shown broad spectrum of antibacterial and antifungal activities. Many scientific groups have synthesized and screened their antimicrobial potential. Reported activity data showed that some 1,3,4-oxadiazole derivatives exhibited better activity than already known antibiotics. Hence, they can be used as lead for development of promising antimicrobial agents. In present review, antimicrobial activities and SAR of 2,5-disubstituted 1,3,4-oxadiazole derivatives reported by different research groups in last ten years have been summarized.

Thiazole or 1,3-thiazole is a distinct heterocyclic compound which incorporates sulphur and nitrogen atoms. It is a vital framework present in numerous pharmacologically active compounds, be it of natural origin or of synthetic nature. Many thiazoles having antitumor and antiviral activities, originate from microbes and marine organisms. A variety of synthetic drugs, having thiazole group, like antimicrobial sulfathiazole, antibiotic penicillin, antidepressant pramipexole, antineoplastic agent bleomycin, antiretroviral drug ritonavir, histamine H 2 receptor antagonist nizatidine, anti-inflammatory drug meloxicam, antifungal stilbene derivatives have been in the markets for quite some time. Hofmann and Hantzsch laid the groundwork for further development in the field of thiazole chemistry. The interaction of α -haloketones or α -halogenaldehyde and thioamide to obtain thiazoles is beautifully described by Hantzsch. Various studies have reported methods for the synthesis of the thiazoles; thioforamide, thiourea, α -thiocyanotoketones, and vinyl bromide have been extensively employed to synthesize thiazoles. The thiazoles have immense potential and this study tries to enlighten the crucial role of thiazoles for the betterment of society. The review provides different directions in the synthesis of novel thiazoles and also reveals diverse targets for augmentation in the field of designing of novel thiazoles.

Thiazolopyrimidine is a nitrogen and sulphur containing heterocyclic aromatic molecule. The bicyclic compound is made by fusing two aromatic rings, thiazole and pyrimidine and replacing one carbon atom with nitrogen and sulphur. The current present work covers a wide range of methods for synthesizing thiazolopyrimidine and its derivatives using a variety of catalysts, solvent medium and microwave irradiation with a goal of achieving a high yield and rapid separation of the product. This article describes the evolution of thiazolopyrimidine as antimicrobial, antiviral, anti-Parkinson, anticancer, anti-inflammatory as well as its structure-activity relationship and potential mode of action for future research. It also includes a list of current patents filed/granted linked to various pharmacological activities in the previous few years.

B-cell lymphoma 2-associated athanogene 3 protein is profoundly expressed in various cancer tissues, which can lead to proliferation, migration and invasion of cancer. The raw data for microarray data analysis was obtained from the dataset record GDS2918. The self-organizing map and k-means of the genesis led to the identification of two clusters containing B-cell lymphoma 2-associated athanogene 3 gene among others; cluster number 1 (consisting of 902 genes) from self-organizing map and cluster number 09 (consisting of 348 genes) from k-means. The post clustering tool, SimGene, of Easy M-A was exploited to establish 84 genes with similar expressions as that of B-cell lymphoma 2-associated athanogene 3. The neighbor-joining method in molecular evolutionary genetics analysis version 5 clearly establishes the evolutionary similarity in between B-cell lymphoma 2-associated athanogene 3 and Small glutamine rich tetratricopeptide repeat containing beta. The EasyModeller was utilized for homology modeling of B-cell lymphoma 2-associated athanogene 3 and Small glutamine rich tetratricopeptide repeat containing beta proteins. The protein data bank files were subjected to Procheck in structural analysis and verification server, which evaluates by Ramachandran plot. The selected models were further subjected to loop modeling and validation. Ligands were identified by using DrugBank and were docked against B-cell lymphoma 2-associated athanogene 3 and Small glutamine rich tetratricopeptide repeat containing beta using AutoDock tool. This led to the identification of two compounds, i.e., DB07503 and DB13715 with potential to modulate B-cell lymphoma 2-associated athanogene 3 and aid in the management of various cancers wherein B-cell lymphoma 2-associated athanogene 3 is profoundly overexpressed.

Antimicrobial agents are essential drugs for the health of humans and animals as they cure infectious diseases produced by several contagious strains (bacteria, fungi, parasites, and viruses). Antibiotics efficacy is restricted by an increased number of antibiotic-resistant bacteria. Computational chemistry is crucial in the development of novel potential therapeutics. In this study, the objective was to integrate the two separately bioactive molecules, i.e., thiazoles and pyrimidines into one molecule to produce compounds with better pharmacological activity. Various thiazolo-pyrimidine derivatives were planned through a suitable synthetic scheme and were docked on DNA gyrase subunit B and dihydrofolate reductase, which are established targets for microbial infection. The results were studied and the findings were compared to two known medications as well as potential inhibitors. The result recognizes few thiazolo-pyrimidine derivatives with increased binding efficiency leading to enhanced potency.

Molecular docking is the identification of ligand’s correct binding geometry i.e. pose in the binding site and estimation of its binding affinity for rational design of drug molecule. The current study endeavored the high throughput in silico screening of 56 derivatives of dihydropyridazin-3(2H)-one docked with human cytosolic branched chain amino transferase using PyRx-virtual screening tool. Out of 56 compounds, almost all the test compounds showed very good binding affinity score. Gabapentin was used as standard drug which shows binding affinity of -6.2. On the basis of H-bond interactions, compounds 3, 9, 11, 25, 26, 31, 34, 39, 47, 48, 51, 54, 56 were found to be potent outcome for anticonvulsant activity. Compounds 11, 25, 39, 56 showed excellent H-bond interactions with protein active site, Among which compound 11 showed the outstanding interactions with acceptable bond length 2.34, 2.57, 2.62, 3.03 Å.

The High Mobility Group A1 (HMGA1) gene over expression has been widely observed in various types of cancers. The raw data for microarray data analysis was obtained from the dataset record GDS3525. The SOM and K-means of the Genesis led to the identification of two clusters (each consisting of 30 genes) bearing HMGA1 gene. This on further analysis resulted into identification of 14 similar genes by Easy M-A. The evolutionary similarity of HMGA1 and GORASP2 is clearly observed in the Phylogenetic Tree. Due to the absence of precise structures, the homology modeling was done by using EasyModeller and the resulting models of proteins HMGA1 and GORASP2 were validated by Ramachandran plot. These models were further put to loop optimization by Modloop and the output models were assessed by Ramachandran plot (Rampage) and through SAVS (Procheck). The molecular docking was done by using Autodock, this resulted in two ligands, DB11641 (Vinflunine) and DB12674 (Lurbinectedin), showing potential for the effective treatment of various types of cancers characterized by the over expression of HMGA1 and GORASP2.

Heterocyclic compounds with thiazole moiety are one of the most promising compounds in the medicinal chemistry possessing numerous therapeutic activities. The present was designed to study the high throughput in silico screening of 10 designed 2-phenyl-amino thiazole derivatives as a potent FABH inhibitor in Molegro virtual docker software (Version 6.0) using 3iL9 as PDB. The docking results showed mol dock score of -90.94 with four hydrogen bonding for the standard drugs griseofulvin, while on the other hand, N-substituted thiazole derivatives S2, S5, S6, S7, S8, and S9 exhibited excellent mol dock score, ranged from -102.612 to -144.236, hydrogen bonding (4-10), and docking score ranged from -104.873 to -143.593. Similarly, another in silico study was done using online PASS software and the compounds S1, S2, S5, S6, S7, S8, and S9 have Pa ranged between 0.310 to 0.411 and showed good antibacterial activity whereas, compounds having Pa ranged between 0.216 to 0.334 demonstrated potent antifungal activity when compared to standard drugs. Thus, the present study affirmed the significant antimicrobial potential of some designed N-substituted thiazole derivatives based on their mol dock values and other parameters when studies in silico and the obtained results will provide data support and offer perspectives in future researches to develop potent antimicrobial agents from these N-substituted thiazole derivatives.

Bombax ceiba plant belongs to bombacaceae family and is commonly known as Semal (Hindi) and Cotton tree (English). It has numerous effects like stimulant, astringent, haemostatic, diuretics, antidiarrhoeal, emeticand antipyretic. Major pharmacological activities reported in this plant are hypoglycemic, antianxiety, antibacterial, antiviral and anti-inflammatory. Numerous side effects and increased resistance to anthelmintic drugs prompted us to discover cost effective safe formulation of conventional medicinal plants. In the present study, research work is focused to evaluate the possible anthelmintic effects of Bombax ceiba. To investigate anthelmintic potential of Bombax ceiba plant, different extracts from dried powder stem bark were tested on adult Indian earthworms (Pheretima posthuma) having physiological & anatomical resemblance with human intestinal roundworm parasites. The drugs were divided in 14 groups consisting of test, standard and control. Each group was consisting of six Indian earthworms of approximately same size. Albendazole was used as standard drug while tween80 in normal saline (1:1) was used as control. The result data reveals that all extracts have significant anthelmintic activity as compared to Albendazole taken as standard drug. The methanolic extract at dose of 50 mg/ml concentration showed paralysis time 30±0.96 minutes and death 33.66±0.71 minutes, which is equivalent to standard drug values at dose of 20 mg/ml. Ethylacetate extract at dose of 50 mg/ml showed paralysis at 28.66±0.71 minutes and death at 34.16±1.10 minutes, which proves that it is even better than standard drug in terms of paralysis time and equipotent in terms of time taken for causing death. Thus among the extracts, ethylacetate and methanolic extracts showed maximum activity with least time taken for paralysis and death of earthworms and were found equally potent as Albendazole at a dose of 50 mg/ml. Thus, Bombax ceiba traditional use in helminitic infestation was proved scientifically. On comparing phytochemical evaluation with anthelmintic activity it is assumed that glycosides may be responsible for this activity. A further investigation may lead development of novel anthelmintic drug or formulation with anthelmintic activity.