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Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies. [ABSTRACT FROM AUTHOR]

Malaria is a serious illness transmitted through the bite of an infected mosquito, which is caused by a type of parasite called plasmodium and can be fatal if left untreated. Thus, newer antimalarials with unique mode of actions are encouraged. Fused pyridines have been vastly reported for numerous pharmacological activities including but not limited to analgesics, antitubercular, antifungal, antibacterial and antiapoptotic agents. In a current study, a series of substituted Imidazo[1,2-a]pyridine-3-carboxamides (IMPCs) (SM-IMP-01-13) along with some hydrazides (DA-01-DA-02) were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR), 1H-/ 1 3 C-NMR (proton/carbon nuclear magnetic resonance), elemental analyses and mass spectra. These synthesized analogies were subjected for in vitro biological activities such as Brine Shrimp lethality (BSL), and assay of β -hematin formation inhibitions. The BSL assay results suggested that compounds, SM-IMP-09, SM-IMP-05 were found to be less toxic and they also had comparable toxicity as of 5-Flurouracil (control) ((e.g., at 10 μ g/ml: 20% deaths of nauplii). Derivatives SM-IMP-02, and DA-05 inhibited β -hematin formation: IC 5 0 : 1.849 and 0.042 μ M, respectively). Our molecular docking analysis on plasmodial cysteine protease falcipain-2 indicated that compound DA-05 (–9.993 kcal/mol) had highest docking score and it was comparable to standard Chloroquine (–7.673 kcal/mol). The most active molecule, DA-05 was also retained with lower HOMO–LUMO energy gap as 3.36 eV. Further, we have also analyzed MEP, and other global reactivity indexes for all IMPCs using DFT. Finally, our in-silico pharmacokinetic analysis suggested that all compounds were having good% human oral absorption values (≈ 100%), good Caco-2 cell permeabilities (>1600 nm/s), and non- carcinogenic profiles. Substituted Imidazo[1,2-a]pyridine-3-carboxamides (IMPCs) and hydrazides were synthesized and characterized for their potential as antimalarial agents. The compounds exhibited promising results in in-vitro assays, with SM-IMP-09 and SM-IMP-05 showing low toxicity and SM-IMP-02 and DA-05 displaying significant inhibition of β-hematin formation. Molecular docking analysis revealed that compound DA-05 had a high docking score comparable to Chloroquine against plasmodial cysteine protease falcipain-2, and in-silico pharmacokinetic analysis indicated favorable properties such as good oral absorption, high cell permeabilities, and non-carcinogenic profiles for all compounds. [ABSTRACT FROM AUTHOR]

In recent years, antimicrobial agents have been crucial in improving public health worldwide. However, due to improper usage, bacteria have developed resistance to these agents. This has led researchers to explore the use of heterocyclic compounds as alternative antimicrobial agents to combat resistance. Considering the success of heterocyclic derivatives in developing effective antimicrobial drugs, we conducted a 2D-QSAR (QSAR models using 2D-descriptors) study on novel pyrimidine derivatives and performed in silico simulations to evaluate their potential antibacterial activity against quinolone-resistant Escherichia coli. We used QSARINS V.2.2 (Insubria) software for the 2D-QSAR analysis and performed in silico absorption, distribution, metabolism, and excretion (ADME) and docking studies on 16 newly designed compounds. The best QSAR model had a high correlation coefficient ( R 2 = 0. 9 6 3 3 , Q LOO 2 = 0. 9 5 3 8 , Q LMO 2 = 0. 9 5 1 3) and showed no outliers. Based on these favorable results, we designed 16 new compounds and predicted their antibacterial activity using the best equation. Amongst the top six designed compounds, which had the best docking scores were subjected to practical synthesis. Compound 3cd was found to be good candidature from in-vitro anti-E. Coli activity. This compound may be targeting the DNA gyrases and thus, have inhibitory activity against E. Coli. This observation was also supported by 100 ns molecular dynamics and normal mode analysis results. The most promising compounds identified through these computational studies may be synthesized and tested as potential new drug candidates for treating bacterial infections. To summarize, we have developed a statistically robust and valid 2D-QSAR model with a set of 51 compounds of antibacterial pyrimidines using QSARINS V.2.2. The model is tested on newly designed fused pyrimidine derivatives for predicting bioactivity. Based on the QSAR model, binding affinity and ADMET prediction results, six designed compounds 3ae, 3af, 3be, 3bf, 3ca, and 3cd can act as a potent DNA gyrase inhibitor. These 4 compounds were synthesized with good yield and screened for antibacterial activity against E. coli. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovarian syndrome (PCOS) is a neuroendocrine metabolic disorder characterized by an irregular menstrual cycle. Treatment for PCOS using synthetic drugs is effective. However, PCOS patients are attracted towards natural remedies due to the effective therapeutic outcomes with natural drugs and the limitations of allopathic medicines. In view of the significance of herbal remedies, herein, we discuss the role of different herbs in PCOS. Methods: By referring to the Scopus, PubMed, Google Scholar, Crossref and Hinari databases, a thorough literature search was conducted and data mining was performed pertaining to the effectiveness of herbal remedies against PCOS. Results: In this review, we discuss the significance of herbal remedies in the treatment of PCOS, and the chemical composition, mechanism of action and therapeutic application of selected herbal drugs against PCOS. Conclusions: The present review will be an excellent resource for researchers working on understanding the role of herbal medicine in PCOS. [ABSTRACT FROM AUTHOR]

Fused pyridines are reported to display various pharmacological activities, such as antipyretic, analgesic, antiprotozoal, antibacterial, antitumor, antifungal, anti-inflammatory, and antiapoptotic. They are widely used in the field of medicinal chemistry. Imidazopyridines (IZPs) are crucial classes of fused heterocycles that are expansively reported on in the literature. Evidence suggests that IZPs, as fused scaffolds, possess more diverse profiles than individual imidazole and pyridine moieties. Bacterial infections and antibacterial resistance are ever-growing risks in the 21st century. Only one IZP, i.e., rifaximin, is available on the market as an antibiotic. In this review, the authors highlight strategies for preparing other IZPs. A particular focus is on the antibacterial profile and structure–activity relationship (SAR) of various synthesized IZP derivatives. This research provides a foundation for the tuning of available compounds to create novel, potent antibacterial agents with fewer side effects. [ABSTRACT FROM AUTHOR]

Diabetes is an endocrinological disorder with a rapidly increasing number of patients globally. Over the last few years, the alarming status of diabetes has become a pivotal factor pertaining to morbidity and mortality among the youth as well as middle-aged people. Current developments in our understanding related to autoimmune responses leading to diabetes have developed a cause for concern in the prospective usage of immunomodulatory agents to prevent diabetes. The mechanism of action of vaccines varies greatly, such as removing autoreactive T cells and inhibiting the interactions between immune cells. Currently, most developed diabetes vaccines have been tested in animal models, while only a few human trials have been completed with positive outcomes. In this review, we investigate the undergoing clinical trial studies for the development of a prototype diabetes vaccine. [ABSTRACT FROM AUTHOR]

Cancer is a life-threatening disease and is the second leading cause of death worldwide. Although many drugs are available for the treatment of cancer, survival outcomes are very low. Hence, rapid development of newer anticancer agents is a prime focus of the medicinal chemistry community. Since the recent past, computational methods have been extensively employed for accelerating the drug discovery process. In view of this, in the present study we performed 2D-QSAR (Quantitative Structure-Activity Relationship) analysis of a series of compounds reported with potential anticancer activity against breast cancer cell line MCF7 using QSARINS software. The best four models exhibited a r2 value of 0.99. From the generated QSAR equations, a series of pyrimidine-coumarin-triazole conjugates were designed and their MCF7 cell inhibitory activities were predicted using the QSAR equations. Furthermore, molecular docking studies were carried out for the designed compounds using AutoDock Vina against dihydrofolate reductase (DHFR), colchicine and vinblastine binding sites of tubulin, the key enzyme targets in breast cancer. The most active compounds identified through these computational studies will be useful for synthesizing and testing them as prospective novel anti-breast cancer agents. [ABSTRACT FROM AUTHOR]

In recent years, g-C3N4 photocatalyst-mediated organic reactions have represented an important mode of chemical transformations and are expected to become a crucial field at the forefront of organic chemistry. Polymeric g-C3N4 as a heterogeneous catalyst has attracted great attention compared to other metal-based catalysts in photocatalytic applications because of its cost-effectiveness, good chemical stability, no heavy metal pollution, and eco-friendliness. In recent years, aerobic oxidation under visible-light has been identified as an attractive and fast-developing field in synthetic chemistry due to the simple operating procedure, easy work up and high efficiency. This review highlights carbon nitride-catalyzed visible-light-promoted strategies for the oxidation of alcohols, synthesis of esters, phenols, and sulfoxides, reduction of nitro compounds, the formation of carbonyl compounds, and several coupling reactions. However, g-C3N4 demands high temperature and O2 pressure in addition to visible-light in the system to deliver the desired organic transformations. An alternative strategy may be to anchor organic dyes on the surface of heterogeneous catalysts for mild reaction conditions. The more challenging reaction is the reduction, since investigations related to the selective photoreduction of organic substrates are limited in comparison with photocatalytic selective oxidation; specifically, g-C3N4 is restricted to nitro compounds predominantly. Attempts can be made to enhance the selectivity in reduction by modifying surfaces, changing external conditions, forming composites, etc. [ABSTRACT FROM AUTHOR]

1,5-Benzothiazepine is an important heterocyclic ring containing benzene ring fused with a seven-membered thiazepine. This ring structure is not only found in a variety of medicinally important therapeutic agents but also enjoy a broad spectrum of bioactivities. Considering its broad bioactivities, in the present work we synthesized novel 1,5-benzothiazepine derivatives by the reaction of isobutyl chalcones with 2-aminothiophenol. The characterization of the compounds was done by physicochemical and spectral analysis (FT-IR, 1H NMR, 13C NMR and MS) and evaluated for their antibacterial and antifungal activities. The compounds with halogen atom showed very promising activity when compared to the commercial drugs, ciprofloxacin and fluconazole. Among the halogens, fluorinated compounds i.e., BT6 exhibited superior antimicrobial activity than the standard drugs with MIC 0.4 μg/mL against all the strains whereas it is active on Escherichia coli at the MIC 0.8 μg/mL. The other fluorinated compound BT5 was the most active compound against Escherichia coli with the MIC 0.4 μg/mL. BT3 with two chlorine atoms shown potent activity with MIC 0.4 μg/mL and 1.6 μg/mL against Staphylococcus aureus and Candida albicans respectively. BT5 was also more active than the standard drugs against Staphylococcus aureus, Proteus vulgaris and Aspergillus niger (MIC 0.8 μg/mL) and Candida tropicalis (1.6 μg/mL). Atom-based 3D-QSAR was carried out using the PHASE module of Schrodinger software to assess the validity of the invitro antimicrobial data. The computational studies were more or less in close harmony with the invitro activity data. The invitro biological activity data and the insilico atom-based 3D-QSAR results provide a set of guiding principles for the designing of compounds with better antibacterial and antifungal properties. [ABSTRACT FROM AUTHOR]

Correction for 'Heterogeneous graphitic carbon nitrides in visible-light-initiated organic transformations' by Santosh Kumar Verma et al., Green Chem., 2022, DOI: 10.1039/d1gc03490a. [ABSTRACT FROM AUTHOR]

Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole–chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC50 = 11 ± 1 µM) with an IC50 value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer. [ABSTRACT FROM AUTHOR]

Despite the availability of many drugs to treat infectious diseases, the problems like narrow antimicrobial spectrum, drug resistance, hypersensitivities and systemic toxicities are hampering their clinical utility. Based on the above facts, in the present study, we designed, synthesized and evaluated the antibacterial and antifungal activity of novel fluorinated compounds comprising of chalcones bearing trifluoromethyl (A1–A10) and trifluoromethoxy (B1–B10) substituents. The compounds were characterized by spectroscopic techniques and evaluated for their antimicrobial activity against four pathogenic Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Escherichia coli and Bacillus subtilis) bacterial and fungal (Candida albicans and Aspergillus niger) strains. In this study, the compounds with trifluoromethoxy group were more effective than those with trifluoromethyl group. Among the 20 fluorinated chalcones, compound A3/B3 bearing an indole ring attached to the olefinic carbon have been proved to possess the most antimicrobial activity compared to the standard drugs without showing cytotoxicity on human normal liver cell line (L02). Further, the minimum inhibitory concentration (MIC) for A3/B3 was determined by serial tube dilution method and showed potential activity. These results would provide promising access to future study about the development of novel agents against bacterial and fungal infections. [ABSTRACT FROM AUTHOR]

Infectious diseases caused by fungi and mycobacteria pose an important problem for humankind. Similarly, cancer is one of the leading causes of death globally. Therefore, there is an urgent need for the development of novel agents to combat the deadly problems of cancer, tuberculosis, and also fungal infections. Hence, in the present study, we designed, synthesized, and characterized 30 compounds including 15 chalcones (2–16) and 15 dihydropyrazoles (17–31) containing dichlorophenyl moiety and also screened these compounds for their antifungal, antitubercular, and antiproliferative activities. Among these compounds, the dihydropyrazoles showed excellent antifungal and antitubercular activities whereas the chalcones exhibited promising antiproliferative activity. Among the dihydropyrazoles, compound 31 containing 2-thienyl moiety showed promising antifungal activity (MIC 5.35 µM), whereas compounds 22 and 24 containing 2,4-difluorophenyl and 4-trifluoromethyl scaffolds revealed significant antitubercular activity with the MICs of 3.96 and 3.67 µM, respectively. Compound 16 containing 2-thienyl moiety in the chalcone series showed the highest anti-proliferative activity with an IC50 value of 17 ± 1 µM. The most active compounds identified through this study could be considered as starting points in the development of drugs with potential antifungal, antitubercular, and antiproliferative activities. [ABSTRACT FROM AUTHOR]

Benzimidazole nucleus is a predominant heterocycle displaying a wide spectrum of pharmacological activities. The privileged nature of the benzimidazole scaffold has been revealed by its presence in most small molecule drugs and in its ability to bind multiple receptors with high affinity. A literature review of the scaffold reveals several instances where structural modifications of the benzimidazole core have resulted in high-affinity lead compounds against a variety of biological targets. Hence, this structural moiety offers opportunities to discover novel, better, safe and highly potent biological agents. The goal of the present review is to compile the medicinal properties of benzimidazole derivatives with a focus on SAR (Structure-Activity Relationships)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is a leading cause of death worldwide and its incidence is unfortunately anticipated to rise in the next years. On the other hand, vascular endothelial growth factor receptor 2 (VEGFR-2) is highly expressed in tumor-associated endothelial cells, where it affects tumor-promoting angiogenesis. Therefore, VEGFR-2 is considered one of the most promising therapeutic targets for cancer treatment. Furthermore, some FDA-approved benzimidazole anthelmintics have already shown potential anticancer activities. Therefore, repurposing them against VEGFR-2 can provide a rapid and effective alternative that can be implicated safely for cancer treatment. Hence, 13 benzimidazole anthelmintic drugs were subjected to molecular docking against the VEGFR-2 receptor. Among the tested compounds, fenbendazole (FBZ, 1 ), mebendazole (MBZ, 2 ), and albendazole (ABZ, 3 ) were proposed as potential VEGFR-2 antagonists. Furthermore, molecular dynamics simulations were carried out at 200 ns, giving more information on their thermodynamic and dynamic properties. Besides, the anticancer activity of the aforementioned drugs was tested in vitro against three different cancer cell lines, including liver cancer (HUH7), lung cancer (A549), and breast cancer (MCF7) cell lines. The results depicted potential cytotoxic activity especially against both HUH7 and A549 cell lines. Furthermore, to improve the aqueous solubility of MBZ, it was formulated in the form of mixed micelles (MMs) which showed an enhanced drug release with better promising cytotoxicity results compared to the crude MBZ. Finally, an in vitro quantification for VEGFR-2 concentration in treated HUH7 cells has been conducted based on the enzyme-linked immunosorbent assay. The results disclosed that FBZ, MBZ, and ABZ significantly ( p < 0.001) reduced the concentration of VEGFR-2, while the lowest inhibition was achieved in MBZ-loaded MMs, which was even much better than the reference drug sorafenib. Collectively, the investigated benzimidazole anthelmintics could be encountered as lead compounds for further structural modifications and thus better anticancer activity, and that was accomplished through studying their structure-activity relationships., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Despite the availability of a variety of chemotherapeutic agents, cancer is still one of the leading causes of death worldwide because of the problems with existing chemotherapeutic agents like objectionable side effects, lack of selectivity, and resistance. Hence, there is an urgent need for the development of novel anticancer agents with high usefulness, fewer side effects, devoid of resistance and superior selectivity., Objective: The objective of this study is to synthesize a series of novel 1,5-benzothiazepine derivatives and evaluate their anticancer activity employing biological and computational methods., Methods: Twenty new benzothiazepines (BT1-BT20) were prepared by condensing different 1-(4- isobutylphenyl)ethanone chalcones with 2-amiothiophenol and evaluated for their anticancer activity by MTT assay against three cell lines including HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer). These compounds were also tested for their inhibitory action against EGFR (Epidermal Growth Factor Receptor) tyrosine kinase enzyme by taking into account of their excellent action against colon and breast cancer cell lines. Further, the structural features responsible for the activity were identified by Pharmacophorebased modelling using Schrodinger's PHASETM software., Results: Among the 20 benzothiazepine derivatives, three compounds viz., BT18, BT19 and BT20 exhibited promising activity against the cell lines tested and the activity of BT20 was more than the standard methotrexate. Again the above three compounds showed excellent inhibitory activity with the percentage inhibition of 64.5, 57.3 and 55.8 respectively against EGFR (Epidermal Growth Factor Receptor) tyrosine kinase. PHASE identified a five-point AHHRR model for the proposed activity and the computational studies provided insights into the structural requirements for the anticancer activity and the results were consistent with the observed in vitro activity data., Conclusion: These novel benzothiazepines will be useful as lead molecules for the further development of new cancer therapies against colon and breast cancers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)