Efficient chromium removal from leather industrial wastewater in batch experimental study: Green synthesis and characterization of zinc oxide nanoparticles using Ficus benghalensis extracts.

The urgent need to address the severe environmental risk posed by chromium-contaminated industrial wastewater necessitates the development of eco-friendly cleanup methodologies. Utilizing the Ficus benghalensis plant extracts, the present study aims to develop green zinc oxide nanoparticles for the removal of Cr metal ions from wastewater. The leaves of Ficus benghalensis, often known as the banyan tree, were used to extract a solution for synthesizing ZnO NPs. These nanoparticles were developed with the goal of efficiently eliminating chromium (Cr) from industrial effluents. Batch studies were carried out to assess the efficiency of these synthesized ZnO NPs in treating leather industrial effluent, with aiming for optimal chromium removal. This involved measuring the nanoparticles' capacity to adsorb Cr ions from wastewater samples by comparing chromium levels before and after treatment. Removal efficiency for Cr was estimated through the batches such as optimization of pH, contact time, initial Cr concentration and sorbent dose of ZnO NPs were of the batches. These synthesized ZnO NPs were found to be successful in lowering chromium levels in wastewater to meet permissible limit. The nanoparticles exhibited their highest absorption capacity, reaching 94 % (46 mg/g) at pH 4, with a contact time of 7 hours with the optimum sorbent dose of 0.6 g/L. Hence, the excellent adsorption capabilities of these nanoparticles, together with their environmentally benign manufacturing technique, provide a long-term and efficient solution for chromium-contaminated wastewater treatment. Its novel nature has the potential to significantly improve the safety and cleanliness of water ecosystems, protecting the both i.e. human health and the environment.

α-Glucosidase inhibitory potential of Oroxylum indicum using molecular docking, molecular dynamics, and in vitro evaluation.

Background: According to the International Diabetes Federation, there will be 578 million individuals worldwide with diabetes by 2030 and 700 million by 2045. One of the promising drug targets to fight diabetes is α-glucosidase (AG), and its inhibitors may be used to manage diabetes by reducing the breakdown of complex carbohydrates into simple sugars. The study aims to identify and validate potential AG inhibitors in natural sources to combat diabetes. Methods: Computational techniques such as structure-based virtual screening and molecular dyncamic simulation were employed to predict potential AG inhibitors from compounds of Oroxylum indicum. Finally, in silico results were validated by in vitro analysis using n-butanol fraction of crude methanol extracts. Results: The XP glide scores of top seven hits OI_13, OI_66, OI_16, OI_44, OI_43, OI_20, OI_78 and acarbose were -14.261, -13.475, -13.074, -13.045, -12.978, -12.659, -12.354 and -12.296 kcal/mol, respectively. These hits demonstrated excellent binding affinity towards AG, surpassing the known AG inhibitor acarbose. The MM-GBSA dG binding energies of OI_13, OI_66, and acarbose were -69.093, -62.950, and -53.055 kcal/mol, respectively. Most of the top hits were glycosides, indicating that active compounds lie in the n-butanol fraction of the extract. The IC50 value for AG inhibition by n-butanol fraction was 248.1 µg/ml, and for that of pure acarbose it was 89.16 µg/ml. The predicted oral absorption rate in humans for the top seven hits was low like acarbose, which favors the use of these compounds as anti-diabetes in the small intestine. Conclusion: In summary, the study provides promising insights into the use of natural compounds derived from O. indicum as potential AG inhibitors to manage diabetes. However, further research, including clinical trials and pharmacological studies, would be necessary to validate their efficacy and safety before clinical use.

Enhancing chromium removal and recovery from industrial wastewater using sustainable and efficient nanomaterial: A review.

Water contamination can be detrimental to the human health due to higher concentration of carcinogenic heavy metals such as chromium (Cr) in the wastewater. Many traditional methods are being employed in wastewater treatment plants for Cr removal to control the environmental impacts. Such methods include ion exchange, coagulation, membrane filtration, and chemical precipitation and microbial degradation. Recent advances in materials science and green chemistry have led to the development of nanomaterial that possess high specific surface areas and multiple functions, making them suitable for removing metals such as Cr from wastewater. Literature shows that the most efficient, effective, clean, and long-lasting approach for removing heavy metals from wastewater involves adsorbing heavy metals onto the surface of nanomaterial. This review assesses the removal methods of Cr from wastewater, advantages and disadvantages of using nanomaterial to remove Cr from wastewater and potential negative impacts on human health. The latest trends and developments in Cr removal strategies using nanomaterial adsorption are also explored in the present review.

BTEAC Catalyzed Ultrasonic-Assisted Synthesis of Bromobenzofuran-Oxadiazoles: Unravelling Anti-HepG-2 Cancer Therapeutic Potential through In Vitro and In Silico Studies.

In this work, BTEAC (benzyl triethylammonium chloride) was employed as a phase transfer catalyst in an improved synthesis (up to 88% yield) of S-alkylated bromobenzofuran-oxadiazole scaffolds BF1-9. These bromobenzofuran-oxadiazole structural hybrids BF1-9 were evaluated in vitro against anti-hepatocellular cancer (HepG2) cell line as well as for their in silico therapeutic potential against six key cancer targets, such as EGFR, PI3K, mTOR, GSK-3ß, AKT, and Tubulin polymerization enzymes. Bromobenzofuran structural motifs BF-2, BF-5, and BF-6 displayed the best anti-cancer potential and with the least cell viabilities (12.72 ± 2.23%, 10.41 ± 0.66%, and 13.08 ± 1.08%), respectively, against HepG2 liver cancer cell line, and they also showed excellent molecular docking scores against EGFR, PI3K, mTOR, and Tubulin polymerization enzymes, which are major cancer targets. Bromobenzofuran-oxadiazoles BF-2, BF-5, and BF-6 displayed excellent binding affinities with the active sites of EGFR, PI3K, mTOR, and Tubulin polymerization enzymes in the molecular docking studies as well as in MMGBSA and MM-PBSA studies. The stable bindings of these structural hybrids BF-2, BF-5, and BF-6 with the enzyme targets EGFR and PI3K were further confirmed by molecular dynamic simulations. These investigations revealed that 2,5-dimethoxy-based bromobenzofuran-oxadiazole BF-5 (10.41 ± 0.66% cell viability) exhibited excellent cytotoxic therapeutic efficacy. Moreover, computational studies also suggested that the EGFR, PI3K, mTOR, and Tubulin polymerization enzymes were the probable targets of this BF-5 scaffold. In silico approaches, such as molecular docking, molecular dynamics simulations, and DFT studies, displayed excellent association with the experimental biological data of bromobenzofuran-oxadiazoles BF1-9. Thus, in silico and in vitro results anticipate that the synthesized bromobenzofuran-oxadiazole hybrid BF-5 possesses prominent anti-liver cancer inhibitory effects and can be used as lead for further investigation for anti-HepG2 liver cancer therapy.

Synthetic Potential of Regio- and Stereoselective Ring Expansion Reactions of Six-Membered Carbo- and Heterocyclic Ring Systems: A Review.

Ring expansion reactions fascinate synthetic chemists owing to their importance in synthesizing biologically active compounds and their efficacy in medicinal chemistry. The present review summarizes a number of synthetic methodologies, including stereoselective and regioselective pathways adopted by scientists, for framing medium- to large-size carbo- and heterocycles involving lactams, lactone, azepine and azulene derivatives via ring expansion of six-membered carbo- and heterocycles that have been reported from 2007-2022. Numerous rearrangement and cycloaddition reactions involving Tiffeneau-Demjanov rearrangement, Aza-Claisen rearrangement, Schmidt rearrangement, Beckmann rearrangement, etc., have been described in this regard.

Synthesis, In Vitro Evaluation and Molecular Docking Studies of Novel Thiophenyl Thiazolyl-Pyridine Hybrids as Potential Anticancer Agents.

Many literature reports revealed the anticancer activity of pyridine and thiazole derivatives, especially in lung cancer. Therefore, a new series of thiazolyl pyridines linked with thiophene moiety via hydrazone group was prepared by one-pot multi-component reaction of (E)-1-(4-methyl-2-(2-(1-(thiophen-2-yl)ethylidene)hydrazinyl)thiazol-5-yl)ethanone with benzaldehyde derivatives and malononitrile in a good yield. Then, compound 5 and the thiazolyl pyridines were investigated for their in vitro anticancer activity against lung cancer (A549) cell line using MTT assay compared to doxorubicin as a reference drug. The structure of all the newly synthesized compounds was established based on spectroscopic data and elemental analyses. For better insight to investigate their mechanism of action on A549 cell line, docking studies were performed, targeting epidermal growth factor receptor (EGFR) tyrosine kinase. The results obtained revealed that the tested compounds displayed excellent anticancer activities against lung cancer cell line except 8c and 8f compared to reference drug. Based on the data obtained, it can be inferred that the novel compounds, as well as their key intermediate, compound 5, demonstrated potent anticancer activity against lung carcinoma by inhibiting EGFR.

A Comprehensive Update of Various Attempts by Medicinal Chemists to Combat COVID-19 through Natural Products.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2-the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins-were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

Theoretical and Anti-Klebsiella pneumoniae Evaluations of Substituted 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide and Imidazopyridine Hydrazide Derivatives.

A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as 1H-NMR, 13C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 suggested that all compounds essentially exhibited activity against selected strains of bacteria. Our DFT analyses suggested that the compounds of the SM-IMP-01-SM-IMP-13 series have HOMO/LUMO gaps within 4.43-4.69 eV, whereas the compounds of the DA-01-DA-05 series have smaller values of the HOMO/LUMO gaps, 3.24-4.17 eV. The lowest value of the global hardness and the highest value of the global softness, 2.215 and 0.226 eV, respectively, characterize the compound SM-IMP-02; thus, it is the most reactive compound in the imidazopyridine carboxamide series (except hydrazide series). This compound also depicted lesser MIC values against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 as 4.8 µg/mL, each. In terms of another series, hydrazide DA-05 depicted strong antimicrobial actions (MIC: 4.8 µg/mL against both bacterial strains) and also had the lowest energy gap (3.24 eV), higher softness (0.309 eV), and lesser hardness (1.62 eV). Overall, when we compare qualitative and quantitative antimicrobial results, it is been very clear that compounds with dibromo substitutions on imidazopyridine (IMP) rings would act as better antimicrobial agents than those with -H at the eighth position on the IMP ring. Furthermore, substituents of higher electronegativities would tend to enhance the biological activities of dibromo-IMP compounds. DFT properties were also well comparable to this trend and overall, we can say that the electronic behavior of compounds under investigation has key roles in their bioactivities.

Pharmacophore Synergism in Diverse Scaffold Clinches in Aurora Kinase B.

Aurora kinase B (AKB) is a crucial signaling kinase with an important role in cell division. Therefore, inhibition of AKB is an attractive approach to the treatment of cancer. In the present work, extensive quantitative structure-activity relationships (QSAR) analysis has been performed using a set of 561 structurally diverse aurora kinase B inhibitors. The Organization for Economic Cooperation and Development (OECD) guidelines were used to develop a QSAR model that has high statistical performance (R2tr = 0.815, Q2LMO = 0.808, R2ex = 0.814, CCCex = 0.899). The seven-variable-based newly developed QSAR model has an excellent balance of external predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The QSAR analysis successfully identifies not only the visible pharmacophoric features but also the hidden features. The analysis indicates that the lipophilic and polar groups-especially the H-bond capable groups-must be present at a specific distance from each other. Moreover, the ring nitrogen and ring carbon atoms play important roles in determining the inhibitory activity for AKB. The analysis effectively captures reported as well as unreported pharmacophoric features. The results of the present analysis are also supported by the reported crystal structures of inhibitors bound to AKB.

Design, Synthesis of New 1,2,4-Triazole/1,3,4-Thiadiazole with Spiroindoline, Imidazo[4,5-b]quinoxaline and Thieno[2,3-d]pyrimidine from Isatin Derivatives as Anticancer Agents.

The current work aims to design and synthesis a new series of isatin derivatives and greatly enhances their cytotoxic activity. The derivatives 3-((bromophenyl) imino)-1-(morpholino (pyridine) methyl) indolin-2-one, 2-((oxoindoline) amino) benzoic acid, 3-(thiazolo-imino) indolinone, ethyl-2-((oxoindolin-3-ylidene)amino)-benzothiophene-3-carboxylate, 1-(oxoindoline)-benzo[4,5] thieno [2,3-d]pyrimidin-4(1H)-one, ethyl-2-(2-oxoindoline) hydrazine-1-carboxylate, N-(mercapto-oxo-pyrimidine)-2-(oxoindoline) hydrazine-1-carboxamide, N-(oxo-thiazolo[3,2-a] pyrimidine)-2-(oxoindolin-ylidene) hydrazine-carboxamide, 3-((amino-phenyl) amino)-3-hydroxy- indolinone, 3-((amino-phenyl) imino)-indolinone, 2-(2-((oxoindoline) amino) phenyl) isoindolinone, 2-(oxoindoline) hydrazine-carbothioamide, 5'-thioxospiro[indoline-3,3'-[1,2,4]triazolidin]-one, 5'-amino-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one and 3-((2-thioxo-imidazo[4,5-b]quinoxaline) imino) indolinone were synthesized from the starting material 1-(morpholino (pyridine) methyl) indoline-2,3-dione and evaluated for their in vitro cytotoxic activity against carcinogenic cells. The new chemical structures were evidenced using spectroscopy (IR, NMR and MS) and elemental analysis. The results show that compounds imidazo[4,5-b]quinoxaline-indolinone, thiazolopyrimidine-oxoindoline, pyrimidine-oxoindoline-hydrazine-carboxamide, spiro[indoline-3,2'-[1,3,4] thiadiazol]-one and spiro[indoline-3,3'-[1,2,4]triazolidin]-one have excellent anti-proliferative activities against different human cancer cell lines such as gastric carcinoma cells (MGC-803), breast adenocarcinoma cells (MCF-7), nasopharyngeal carcinoma cells (CNE2) and oral carcinoma cells (KB).

Highly Selective Methodology for Entrapment and Subsequent Removal of Cobalt (II) Ions under Optimized Conditions by Micellar-Enhanced Ultrafiltration.

Micellar-enhanced ultrafiltration (MEUF), being a separation technique, was used to remove cobalt metal ion (Co2+) from their aqueous solutions in an application to reduce the toxicity level from industrial effluents using a micellar solution of anionic and cationic surfactants. The metal ions were first adsorbed by using anionic surfactants, i.e., sodium dodecyl sulfate (SDS) and sodium oleate (SO). The calculations for partition (Kx) and binding constants (Kb) and their respective free energy of partition and binding (ΔGp and ΔGb kJmol-1) helped significantly to find out the extent of binding or interaction of Co2+ with the surfactant and ΔGp and ΔGb were found to be -29.50 and -19.38 kJmol-1 for SDS and -23.95 and -12.67 kJmol-1 in the case of SO. MEUF work was also performed to find out the optimal conditions to remove metal pollutants from the aqueous system. For the said purpose, various factors and concentrations effect were studied, such as the concentration of the surfactant, concentration of the electrolyte (NaCl), transmembrane pressure, RPM, and pH. The efficiency of this process was checked by calculating various parameters, such as rejection percentage (R%) and permeate flux (J). A maximum rejection of 99.95% with SDS and 99.99% with SO was attained.

Synthesis of Novel N-Methylmorpholine-Substituted Benzimidazolium Salts as Potential α-Glucosidase Inhibitors.

The α-glucosidase enzyme, located in the brush border of the small intestine, is responsible for overall glycemic control in the body. It hydrolyses the 1,4-linkage in the carbohydrates to form blood-absorbable monosaccharides that ultimately increase the blood glucose level. α-Glucosidase inhibitors (AGIs) can reduce hydrolytic activity and help to control type 2 diabetes. Aiming to achieve this, a novel series of 1-benzyl-3-((2-substitutedphenyl)amino)-2-oxoethyl)-2-(morpholinomethyl)-1H-benzimidazol-3-ium chloride was synthesized and screened for its α-glucosidase inhibitory potential. Compounds 5d, 5f, 5g, 5h and 5k exhibited better α-glucosidase inhibitions compared to the standard drug (acarbose IC50 = 58.8 ± 0.012 µM) with IC50 values of 15 ± 0.030, 19 ± 0.060, 25 ± 0.106, 21 ± 0.07 and 26 ± 0.035 µM, respectively. Furthermore, the molecular docking studies explored the mechanism of enzyme inhibitions by different 1,2,3-trisubstituted benzimidazolium salts via significant ligand-receptor interactions.

QSAR Evaluations to Unravel the Structural Features in Lysine-Specific Histone Demethylase 1A Inhibitors for Novel Anticancer Lead Development Supported by Molecular Docking, MD Simulation and MMGBSA.

Using 84 structurally diverse and experimentally validated LSD1/KDM1A inhibitors, quantitative structure-activity relationship (QSAR) models were built by OECD requirements. In the QSAR analysis, certainly significant and understated pharmacophoric features were identified as critical for LSD1 inhibition, such as a ring Carbon atom with exactly six bonds from a Nitrogen atom, partial charges of lipophilic atoms within eight bonds from a ring Sulphur atom, a non-ring Oxygen atom exactly nine bonds from the amide Nitrogen, etc. The genetic algorithm-multi-linear regression (GA-MLR) and double cross-validation criteria were used to create robust QSAR models with high predictability. In this study, two QSAR models were developed, with fitting parameters like R2 = 0.83-0.81, F = 61.22-67.96, internal validation parameters such as Q2LOO = 0.79-0.77, Q2LMO = 0.78-0.76, CCCcv = 0.89-0.88, and external validation parameters such as, R2ext = 0.82 and CCCex = 0.90. In terms of mechanistic interpretation and statistical analysis, both QSAR models are well-balanced. Furthermore, utilizing the pharmacophoric features revealed by QSAR modelling, molecular docking experiments corroborated with the most active compound's binding to the LSD1 receptor. The docking results are then refined using Molecular dynamic simulation and MMGBSA analysis. As a consequence, the findings of the study can be used to produce LSD1/KDM1A inhibitors as anticancer leads.

Development of Ion Character Property Relationship (IC-PR) for Removal of 13-Metal Ions by Employing a Novel Green Adsorbent Aerva javanica.

The novel Aerva javanica absorbent was applied for the removal of thirteen selected metal ions from a distilled water solution of each metal by the batch adsorption method. The optimization remediation parameters of the metal ions for the batch adsorption approach were developed, which were the initial concentrations (60 ppm), contact time (60 min) and pH (7). The basic properties of metal ion affected the adsorption results; therefore, 21 properties of metal ions were selected, which are called "descriptors". The most significant descriptors were selected that were vital for the adsorption results, such as covalent index, polarizability and ion charge. The developed model equation by the descriptors provided more than 80% accuracy in the predicted results. Furthermore, Freundlich and Langmuir adsorption models were also applied on the results. Constants of the Freundlich and Langmuir models were also used for model generation, and the results revealed the importance of a covalent index for the removal phenomenon of metal ions. The current study provided a suitable Ion Character Property Relationship (IC-PR) for the removal of metal ions, and future predictions can be achieved on the proposed adsorbent with significant accuracy. The ecofriendly and cost effective Aerva javanica absorbent in the batch experimental model of the current study predicted that this novel absorbent can be used for the removal of a wide spectrum of heavy metal ions from different sources of waste waters.

QSAR, Molecular Docking, MD Simulation and MMGBSA Calculations Approaches to Recognize Concealed Pharmacophoric Features Requisite for the Optimization of ALK Tyrosine Kinase Inhibitors as Anticancer Leads.

ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm−multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69−0.87, F = 403.46−292.11, etc., internal validation parameters; Q2LOO = 0.69−0.86, Q2LMO = 0.69−0.86, CCCcv = 0.82−0.93, etc., or external validation parameters Q2F1 = 0.64−0.82, Q2F2 = 0.63−0.82, Q2F3 = 0.65−0.81, R2ext = 0.65−0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.

Mechanistic and Predictive QSAR Analysis of Diverse Molecules to Capture Salient and Hidden Pharmacophores for Anti-Thrombotic Activity.

Thrombosis is a life-threatening disease with a high mortality rate in many countries. Even though anti-thrombotic drugs are available, their serious side effects compel the search for safer drugs. In search of a safer anti-thrombotic drug, Quantitative Structure-Activity Relationship (QSAR) could be useful to identify crucial pharmacophoric features. The present work is based on a larger data set comprising 1121 diverse compounds to develop a QSAR model having a balance of acceptable predictive ability (Predictive QSAR) and mechanistic interpretation (Mechanistic QSAR). The developed six parametric model fulfils the recommended values for internal and external validation along with Y-randomization parameters such as R2tr = 0.831, Q2LMO = 0.828, R2ex = 0.783. The present analysis reveals that anti-thrombotic activity is found to be correlated with concealed structural traits such as positively charged ring carbon atoms, specific combination of aromatic Nitrogen and sp2-hybridized carbon atoms, etc. Thus, the model captured reported as well as novel pharmacophoric features. The results of QSAR analysis are further vindicated by reported crystal structures of compounds with factor Xa. The analysis led to the identification of useful novel pharmacophoric features, which could be used for future optimization of lead compounds.

Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives.

In this article, we showed the synthesis of new polycyclic aromatic compounds, such as thienotriazolopyrimidinones, N-(thienotriazolopyrimidine) acetamide, 2-mercapto-thienotriazolo-pyrimidinones, 2-(((thieno-triazolopyrimidine) methyl) thio) thieno-triazolopyrimidines, thieno-pyrimidotriazolo-thiazines, pyrrolo-triazolo-thienopyrimidines, thienopyrimido-triazolopyrrolo-quinoxalines, thienopyrimido-triazolo-pyrrolo-oxathiino-quinoxalinones, 1,4-oxathiino-pyrrolo- triazolothienopyrimidinones, imidazopyrrolotriazolothienopyrimidines and 1,2,4-triazoloimidazo- pyrrolotriazolothienopyrimidindiones, based on the starting material 2,3-diamino-6-benzoyl-5- methylthieno[2,3-d]pyrimidin-4(3H)-one (3). The chemical structures were confirmed using many spectroscopic ways (IR, 1H, 13C, -NMR and MS) and elemental analyses. A series of thiazine, imidazole, pyrrole, thienotriazolopyrimidine derivatives were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines, i.e., CNE2 (nasopharyngeal), KB (oral), MCF-7 (breast) and MGC-803 (gastric) carcinoma cells. The compounds 20, 19, 17, 16 and 11 showed significant cytotoxicity against types of human cancer cell lines.

QSAR and Pharmacophore Modeling of Nitrogen Heterocycles as Potent Human N-Myristoyltransferase (Hs-NMT) Inhibitors.

N-myristoyltransferase (NMT) is an important eukaryotic monomeric enzyme which has emerged as an attractive target for developing a drug for cancer, leishmaniasis, ischemia-reperfusion injury, malaria, inflammation, etc. In the present work, statistically robust machine leaning models (QSAR (Quantitative Structure-Activity Relationship) approach) for Human NMT (Hs-NMT) inhibitory has been performed for a dataset of 309 Nitrogen heterocycles screened for NMT inhibitory activity. Hundreds of QSAR models were derived. Of these, the model 1 and 2 were chosen as they not only fulfil the recommended values for a good number of validation parameters (e.g., R2 = 0.77-0.79, Q2LMO = 0.75-0.76, CCCex = 0.86-0.87, Q2-F3 = 0.74-0.76, etc.) but also provide useful insights into the structural features that sway the Hs-NMT inhibitory activity of Nitrogen heterocycles. That is, they have an acceptable equipoise of descriptive and predictive qualities as per Organisation for Economic Co-operation and Development (OECD) guidelines. The developed QSAR models identified a good number of molecular descriptors like solvent accessible surface area of all atoms having specific partial charge, absolute surface area of Carbon atoms, etc. as important features to be considered in future optimizations. In addition, pharmacophore modeling has been performed to get additional insight into the pharmacophoric features, which provided additional results.

Quantitative Structure-Activity Relationship Evaluation of MDA-MB-231 Cell Anti-Proliferative Leads.

In the present endeavor, for the dataset of 219 in vitro MDA-MB-231 TNBC cell antagonists, a (QSAR) quantitative structure-activity relationships model has been carried out. The quantitative and explicative assessments were performed to identify inconspicuous yet pre-eminent structural features that govern the anti-tumor activity of these compounds. GA-MLR (genetic algorithm multi-linear regression) methodology was employed to build statistically robust and highly predictive multiple QSAR models, abiding by the OECD guidelines. Thoroughly validated QSAR models attained values for various statistical parameters well above the threshold values (i.e., R2 = 0.79, Q2LOO = 0.77, Q2LMO = 0.76-0.77, Q2-Fn = 0.72-0.76). Both de novo QSAR models have a sound balance of descriptive and statistical approaches. Decidedly, these QSAR models are serviceable in the development of MDA-MB-231 TNBC cell antagonists.

Synthesis of antimicrobial azoloazines and molecular docking for inhibiting COVID-19.

Diverse new azoloazines were synthesized from the reaction of fluorinated hydrazonoyl chlorides with heterocyclic thiones, 1,8-diaminonaphthalene, ketene aminal derivatives, and 4-amino-5-triflouromethyl-1,2,4-triazole-2-thiol. The mechanistic pathways and the structures of all synthesized derivatives were discussed and assured based on the available spectral data. The synthesized azoloazine derivatives were evaluated for their antifungal and antibacterial activities through zone of inhibition measurement. The results revealed promising antifungal activities for compounds 4, 5, 17a,b, 19, and 25 against the pathogenic fungal strains used; Aspergillus flavus and Candida albicans compared to ketoconazole. In addition, compounds 4, 5, 19, and 25 showed moderate antibacterial activities against most tested bacterial strains. Molecular docking studies of the promising compounds were carried out on leucyl-tRNA synthetase active site of Candida albicans, suggesting good binding in the active site forming stable complexes. Moreover, docking of the synthesized compounds was performed on the active site of SARS-CoV-2 3CLpro to predict their potential as a hopeful anti-COVID and to investigate their binding pattern.