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Drugs and related goods are widely used in order to promote public health and the quality of life. One of the most serious environmental challenges affecting public health is the ongoing presence of antibiotics in the effluents generated by pharmaceutical industries and hospitals. Antibiotics cannot be entirely removed from wastewater using the traditional wastewater treatment methods. Unmetabolized antibiotics generated by humans can be found in urban and livestock effluent. The antibiotic present in effluent contributes to issues with resistance to antibiotics and the creation of superbugs. Over the recent 2 years, the coronavirus disease 2019 pandemic has substantially boosted hospital waste volume. In this situation, a detailed literature review was conducted to highlight the harmful effects of untreated hospital waste and outline the best approaches to manage it. Approximately 50 to 70% of the emerging contaminants prevalent in the hospital wastewater can be removed using traditional treatment strategies. This paper emphasizes the numerous treatment approaches for effectively eliminating emerging contaminants and antibiotics from hospital wastewater and provides an overview of global hospital wastewater legislation and guidelines on hospital wastewater administration. Around 90% of ECs might be eliminated by biological or physical treatment techniques when used in conjunction with modern oxidation techniques. According to this research, hybrid methods are the best approach for removing antibiotics and ECs from hospital wastewater. The document outlines the many features of effective hospital waste management and might be helpful during and after the coronavirus disease 2019 outbreak, when waste creation on all hospitals throughout the globe has considerably increased.

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A typographical error appeared in author's affiliation in the article titled "N-unsubstituted Imidazoles: Design, Synthesis, and Antimicrobial Evaluation", published in Current Pharmaceutical Design, 2023; 29(23): 1875-1881 [1]. Details of the error and a correction are provided below. Original: Author Affiliation: 1Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Islamic Azad Medical Sciences University, Tehran, Iran. Corrected: Author Affiliation: 1Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. We regret the error and apologize to readers. The original article can be found online at: https://www.eurekaselect.com/article/133413.

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BACKGROUND: All the current antifungal azoles have one substituted nitrogen atom in their imidazole or triazole rings. In this study, eleven imine and amine derivatives of imidazole, in which both nitrogen atoms of the imidazole ring are unsubstituted, were designed and synthesized. MATERIALS AND METHODS: Imine derivatives were prepared by condensation of imidazole-4-carboxaldehyde with appropriate amines, and then in the next step, using sodium borohydride, the imines were reduced to amine derivatives. Docking studies reveal unsubstituted nitrogen atom of the imidazole ring coordinated well with the heme molecule of the receptor. In vitro, antimicrobial evaluation was tested on Candida albicans, E. coli, and Staphylococcus aureus. RESULTS: Based on the results of the antimicrobial study, compound 10, which contains 4-chlorobenzyl moiety, proved to be the most potent compound against Candida albicans, and it was more active than the reference drug fluconazole and showed comparable activity to amphotericin B. Compounds 10 and 11 and compounds 8, 10 and 11 showed significant responses against E. coli and Staphylococcus aureus respectively. CONCLUSION: It is concluded that compound 10 can be acted as a new lead compound to find new azoles antifungal.

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BACKGROUND: Based on the anti-inflammatory and analgesic activity of hydrazone and phthalimide, a new series of hybrid hydrazone and phthalimide pharmacophores was prepared and evaluated as analgesic agents. METHODS: The designed ligands were synthesized by reaction of the appropriate aldehydes and 2- aminophthalimide. Analgesic, cyclooxygenase inhibitory, and cytostatic activity of prepared compounds were measured. RESULTS: All the tested ligands demonstrated significant analgesic activity. Moreover, compounds 3i and 3h were the most potent ligands in the formalin and writhing tests, respectively. Compounds 3g, 3j, and 3l were the most COX-2 selective ligands and ligand 3e was the most potent COX inhibitor with a 0.79 of COX-2 selectivity ratio. The presence of electron-withdrawing moieties with hydrogen bonding ability at the meta position was found to affect the selectivity efficiently, in which compounds 3g, 3l, and 3k showed high COX-2 selectivity, and compound 3k was the most potent one. The cytostatic activity of selected ligands demonstrated that compounds 3e, 3f, 3h, 3k, and 3m showed good analgesic and COX inhibitory activity and were less toxic than the reference drug. CONCLUSION: High therapeutic index of these ligands is one of the valuable advantages of these compounds.

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BACKGROUND: A series of phthalimides related to thalidomide have been studied for analgesic activity in the formalin test. The formalin test was performed in mice in a nociceptive pattern to evaluate analgesic activity. METHODS: In this study, nine derivatives of phthalimides were evaluated in terms of exerting analgesic effects in mice. They exerted significant analgesic effects compared to indomethacin and negative control. These compounds were synthesized and characterized by TLC, followed by IR and H1NMR in the previous studies. Two distinct periods of high licking activity were used to analyze both acute and chronic pain. All compounds were compared with indomethacin and carbamazepine as positive control and vehicle as a negative control. RESULTS: All of the tested compounds exhibited significant analgesic activity in both the first and second phases of the test compared to the control group (DMSO), although they did not show more activity than the reference drug (indomethacin) but were comparable to indomethacin. CONCLUSION: This information may be useful in the development of a more potent phthalimide as an analgesic agent that acts as a sodium channel blocker and COX inhibitor.

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PURPOSE: Oxidative stress can damage cells and cause age-related illnesses such as Alzheimer's, Parkinson's, and Huntington's. This study looked at newly synthesized isoindole derivatives and their effects on SH-SY5Y as a neuroblastoma cell under oxidative stress through the NRF2 signaling pathway. NRF2 transcription factor plays a vital role in the oxidative stress response and cellular homeostasis. METHOD: Three isoindoline-dione derivatives were synthesized by reacting phthalic anhydrides with 4-(2-aminoethyl)-1-benzyl piperidine. Their structures were confirmed through FT-IR, NMR, and Mass spectroscopy. The derivatives were then tested on human SH-SY5Y cells under an oxidative stress model induced by hydrogen peroxide (H2O2). The cell viability, ROS levels, protein carbonyl content, and gene expression of NRF2 and phase II antioxidative enzymes were measured after 24 h. RESULTS: Three isoindoline derivatives (3a-3c) were observed to increase the viability of SH-SY5Y cells by protective against oxidative stress, reducing intracellular reactive oxygen species and carbonylated proteins, and increasing gene expression levels of NRF2 and associated genes such as NQO-1, and GSTK1. CONCLUSION: Isoindoline derivatives demonstrated a neuroprotective effect on SH-SY5Y cells through various neuroprotective mechanisms, although more studies are needed.

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Indole and its derivatives are common heterocyclic compounds in nature that have a wider range of medicinal activities such as antifungal, anti-inflammatory, and anti-seizure. Virtually all indole derivatives showed outstanding antifungal activity against Candida albicans. The aim of this study was to QSAR modeling of indole derivatives and the design of new drugs that have antifungal activity. In this study, 52 compounds were selected. All optimized compounds and quantum descriptors were obtained using Gaussian software and DFT/B3LYP computational method with 6-31 G (d) basis set al, so other descriptors were determined using Dragon software. To examine the relationship between these descriptors and the activity of these compounds, the MLR linear correlation method was used, and the QSAR equation with R2 = 0.7884 and R = 0.8879 was obtained for it. Likewise, MSE = 0.1897, RMSE = 0.2848, and Q2 = 0.68663 approve the acceptability of the obtained model. The obtained equation reveals that the activity of these compounds is related to the negative coefficient of GATS8p, R7e +, and G2e, which means that with increasing the values ​​of these description nodes, the amount of activity declines. On the other hand, the activity of these compounds depended on the positive coefficients of HATS3p, MATS5e, and RDF045, i.e. with increasing these values, the activity of these compounds also increases, and a good correlation was obtained between the experimental and predicted activity values.

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BACKGROUND AND OBJECTIVE: Phthalimide, as the rigid form of ameltolide, exhibits a phenytoin-like profile of drug-receptor interaction and is active in the MES model and inactive in the PTZ model as an anti-epileptic agent. In this research, based on the isosteric replacement, we reported the design, preparation, and antiepileptic activity of 13 new analogs of pyrrolopyridine and isoindole. METHODS: The designed compounds were prepared by condensing 3, 4-pyridine dicarboxylic anhydride, or 4-fluorophthalic anhydride with different aryl amines. MES and PTZ-induced seizure models were utilized to evaluate the antiepileptic effect of the prepared ligands. RESULTS: It was found that the prepared ligands have significantly affected both tonic and clonic seizures. In tonic seizures, the prepared compounds decreased mortality to a significant extent, and in clonic seizures, they significantly showed better frequency and latency. Compounds 9, 12, and 13 were the most potent ligands than phenytoin. CONCLUSION: It is concluded that the best distance between two aryl parts is two bonds, and the substitution of the nitro group at the meta position of the phenyl ring is better than the para position. Our research group has investigated this concept for designing newer compounds with better anticonvulsant activity.

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OBJECTIVE: Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). Nearly all azole antifungal agents are Nsubstituted azoles. In addition, an azolylphenalkyl pharmacophore is uniquely shared by all azole antifungals. Due to the importance of nitrogen atom of azoles (N-3 of imidazole and N-4 of triazole) in coordination with heme in the binding site of the enzyme, here a group of N- un-substituted azoles in which both nitrogen are un-substituted was reported. MATERIALS AND METHODS: Designed compounds were synthesized by the reaction of imidazole-4- carboxaldehyde with appropriate arylamines and subsequently reduced to desired amine derivatives. Antifungal activity against Candida albicans and Saccharomyces cervisiae was done using a broth micro-dilution assay. Docking studies were done using AutoDock. RESULTS: Antimicrobial evaluation revealed that some of these compounds exhibited moderate antimicrobial activities against tested pathogenic fungi, wherein compounds 3, 7, and 8 were potent. Docking studies propose that all of the prepared azoles interacted with 14α-DM, wherein azoleheme coordination played the main role in drug-receptor interaction. CONCLUSION: Our results offer some useful references for molecular design performance or modification of this series of compounds as a lead compound to discover new and potent antimicrobial agents.

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BACKGROUND AND OBJECTIVE: N-aryl derivatives of phthalimide and 4-nitro phthalimide have demonstrated cyclooxygenase inhibitory activity. Also, they possess excellent analgesic and antiinflammatory activity. In this work, a new series of N-arylmethylideneamino derivatives of phthalimide and 4-nitro phthalimide were designed and synthesized. METHODS: The designed compounds were synthesized by condensation of the appropriate aldehyde and N-aminophthalimide in ethanol at room temperature at PH around 3. Their analgesic and antiinflammatory activity were evaluated by acetic acid-induced pain test and carrageenan-induced paw edema test in mice and rats, respectively. RESULTS AND CONCLUSION: The details of the synthesis and chemical characterization of the analogs are described. In vivo screening showed compounds 3a, 3b, 3f and 3h were the most potent analgesic compounds. In addition, compounds 3a, 3c, 3d, 3e and 3j indicated comparable anti-inflammatory activity to indomethacin as a reference drug.

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Anticonvulsant activity of phthalimide was discovered in 2000 by molecular hybridization of thalidomide and ameltolide. In our present research we report some new 4-substituted derivatives of phthalimide with good activity against the tonic and clonic seizures. A series of novel 4-flurophthalimides designed using bioisosteric replacement were synthesized by condensation of 4-flurophthalic anhydride with appropriate arylamines. The purity of these compounds was determined by TLC and the chemical structures were confirmed by IR and 1H-NMR spectroscopy. Anticonvulsant activity of prepared compounds was evaluated using MES and PTZ models. Some of the designed compounds significantly protected mice against the PTZ-induced seizure among which, compound 10 with lipophilic and flexible aromatic moiety was more potent than the reference drug phenytoin and was the most potent in this series of phthalimide derivatives. In the MES model, the prepared phthalimide did not show efficient activity. The prepared compounds are active in clonic seizure.

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BACKGROUND: Hydroxyurea (HU) is used to treat cancer. HU has a short half-life due to its small molecular weight and high polarity, therefore a high dosage of the drug should be used which introduces side effects and more rapid development of resistance. OBJECTIVE: The objective of the current study is to design new lipophilic analogues of hydroxyurea with higher stability and better cell penetration. The designed compounds were synthesized and then evaluated in terms of their cytostatic activities against two human cell lines. METHODS: The synthesis of designed ligands was achieved via two-step procedure. Detail of the synthesis and chemical characterization of the analogs are described. The cytotoxic activity of the designed ligands was evaluated in vitro against two different cancer cell lines at 24 and 48h using MTT test. RESULTS: Based on the IC50 values, all the designed and prepared compounds were more potent than hydroxyurea at 24 and 48h on both cell lines that the cytostatic activity at 48h was more than 24h. Drug-receptor interactions study indicated compound 7 as the most potent ligand, tightly bonded to surrounding amino acids in the active site of receptor via two strong hydrogen bonds and some hydrophobic interactions. CONCLUSION: Compound 7 with the suitable volume, log p and shape is the most active ligand against both cell lines. It is concluded or suggested that the size, shape and hydrophobic character of substituents strongly affect the pharmacodynamics and pharmacokinetics of these type of ligands.

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INTRODUCTION: In this study, fifteen new 2,5-disubstituted analgouges of phthalimide were designed and synthesized using the appropriate synthetic route to evaluate anticonvulsant activity against the Maximal Electroshock (MES) and subcutaneous Pentylenetetrazole (scPTZ) compare to phenytoin as a positive control. The structures of the synthesized compounds were confirmed by FTIR, H-NMR, C-NMR and MASS spectroscopy. METHODS: All the tested compounds were found to be effective in the PTZ model at dose of 60 mg/kg and most of the compounds showed protection against MES test indicative of their ability to inhibit the seizure spread at all dose ranges. Compound 3 illustrated the best efficacy among all compounds and showed more potency than phenytoin in clonic seizure and was potent as phenytoin in tonic seizure. RESULTS & DISCUSSION: Using a model of the Na channel, these derivatives were docked in the active site. Docking studies displayed that all synthesized compounds have more negative binding energy compare to reference drug and inhibition-constant less than phenytoin that means they can block the receptor more efficiently and usually form hydrophobic interactions or hydrogen bond interaction frequently with the domains I, II, III and rarely with domain IV.

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BACKGROUND: Tuberculosis is one of the main medical problems and some people are suffering still from this infectious disease. 1, 4-dihydropyridines are multi-target ligands that recently are recognized as anti-tubercular agents. METHODS: In the current research, computational studies were conducted of some synthesized 1, 4- dihydropyridine-3, 5-dicarboxamides in non-hydrolyzed and hydrolyzed forms to find the drugreceptor interactions profile. RESULTS: Among equations obtained for non-hydrolyzed compounds, the model with better statistical parameters such as R2= 0.9462, q2 of LOO= 0.8318 and q2 of LMO= 0.7987 was considered as the best one and EEig08d, LAI, Mor23m, GATS3e, Mor28m descriptors were identified as the most significant factors that affect the biological activity of non-hydrolyzed compounds. CONCLUSION: In the hydrolyzed compounds, the model which has R2= 0.9731, q2 of LOO= 0.91154462 and q2 of LMO= 0.742 was considered as the best one and Mor27e and BEHv2 were also revealed as the most important descriptors in hydrolyzed compounds.

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Epilepsy is a chronic disorder of the brain affecting around 50 million people in the world. Up to 30% of epileptic patients do not respond to available drugs and medical therapies. In this paper, anticonvulsant screening of 10 synthesized new derivatives of 1, 4-dihydropyridine-3, 5-dicarboxamides was performed. Anticonvulsant activity was evaluated by intravenous and intraperitoneal pentylenetetrazole and maximal electroshock induced seizures tests. Nifedipine was used as reference drug. Our pharmacological results revealing the compounds 2, 4, 5, and 6 can be effective in both absence and grandmal seizures in human. These pharmacological studies have displayed that these new dihydropyridine derivatives are capable to inhibiting seizures induced by pentylenetetrazole and maximal electroshock in mice efficiently.

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OBJECTIVES: Phthalimide-based derivatives have anticonvulsant activity like as phenytoin by inhibition of sodium channel. In our previously research we mentioned about some phthalimide derivatives as potent anticonvulsant agents. MATERIALS AND METHODS: Fourteen analogs of 2-substituted phthalimide pharmacophore were synthesized and then were evaluated for the anticonvulsant activities in pentylenetetrazole-induced seizures (PTZ) and maximal electroshock seizure (MES) models. RESULTS: The in vivo screening results showed that all the analogs have the ability to protect against the maximal electroshock and PTZ. The compounds 3 and 9 elevated clonic seizure thresholds at 30 min which were more active than the standard medicine phenytoin. Compounds 3, 6, 7, 11, 13 and 14 with 100% protection were the most potent ones in tonic seizure. The most potent compound in the both PTZ and MES models was compound 3. Using a model of the open pore of sodium channel, all of the compounds were docked. Results of docking showed that the ligands interacted mainly with residues II-S6 of NaV1.2 by making hydrogen bonds and have additional hydrophobic interactions with other domains in the channel's inner pore. CONCLUSION: Some of these compounds are more potent than phenytoin simultaneously in the clonic and tonic seizures.

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A series of compounds related to ameltolide were studied for anticonvulsant potential in the subcutaneous pentylenetetrazol (sc Ptz) test in mice. These compounds were synthesized and characterized by TLC followed by IR and H1NMR. In-vivo screening data acquired indicate that most of analogs have the ability to protect against PTZ-induced seizure. Phenytoin (PHT) was employed as the reference prototype antiepileptic drug. All compounds exerted their maximal effects 30 min after administration. Out of the 6 compounds, compound 2 at 40 mg/Kg dose is more potent than phenytoin (reference drug) on clonic seizure. Using a model of the open pore of the Na channel, docking study was performed by AutoDock 4.2 program. Docking study has revealed that these compounds are stabilized through at least one hydrogen bond rises from ketone of phthalimide and residue Thr-87 of domain G of sodium channel.

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Piroxicam has two different crystalline forms (known as needle and cubic forms), that they are different in physicochemical properties such as biological solubility. In the current research, using Taguchi experimental design approach the influences of five operating variables on formation of the piroxicam polymorph shapes in recrystallization were studied. The variables include type of solvent, cooling methods, type of mixture paddle, pH, and agitator speed. Statistical analysis of results revealed the significance order of factors affecting the product quality and quantity. At first using the Taguchi experimental method, the influence of process factors on the yield, particle size and dissolution rate of piroxicam powder was statistically investigated. The optimum conditions to achieve the best dissolution rate of piroxicam were determined experimentally. The results were analyzed using Qualitek4 software and it was revealed that the type of solvent and method of cooling respectively are the most important factors that affect the dissolution rate. It was also experimentally achieved that some factors such as type of agitator paddle, pH and agitation rate have no significant effects on dissolution rate.

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BACKGROUND: Selenocyanate derivatives have been recently presented as potent anti-leishmanial agents. OBJECTIVE: In this research, thirty five selenocyanate and diselenide compounds were subjected to docking studies and compared to Edelfosine and Miltefosine as reference drugs and then molecular dynamics (MD) simulation analysis. METHODS: Desired Selenocyanates were built using the HyperChem program and docking calculations were performed on the crystal structure of trypanothione reductase from Leishmania infantum. Then, MD simulation analysis was performed to explore the interaction stability of selected compound during structural motions of the interacting molecules. RESULTS: Based on the binding energy, all of the aryl rings were more potent than Edelfosine and Miltefosine as reference drug. The best compound base on hydrogen bonding, π-π interactions and orientation within the active site with high binding energy was selected for MD simulation analysis. The selected compound is known as high-affinity selective inhibitor for trypanothione reductase. CONCLUSION: These results can be used for future synthesis of new antileishmanial agents with better potency.

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BACKGROUND: Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. OBJECTIVE: In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of hydroxyurea in RNR inhibition as anticancer agent. METHOD: The binding affinity of hydroxyurea and compound III to RNR was studied by docking method. The docking study was performed for the crystal structure of human RNR with the radical scavenger Hydroxyurea and its oxidized form to inhibit the human RNR. hydroxyurea and compound III bind at the active site with Tyr-176, which are essential for free radical formation. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2. To confirm the binding mode of inhibitors, the molecular dynamics (MD) simulations were performed using GROMACS 4.5.5, based upon the docked conformation of inhibitors. RESULTS: Both of the studied compounds stayed in the active site. The results of MD simulations confirmed the binding mode of ligands, accuracy of docking and the reliability of active conformations which were obtained by AutoDock. CONCLUSION: MD studies confirm our proposed mechanism in which compound III reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme.

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