Biochemical and computational inhibition of α-glucosidase by novel metronidazole-linked 1H-1,2,3-triazole and carboxylate moieties: kinetics and dynamic investigations.

In the current study, metronidazole derivatives containing 1H-1,2,3-triazole and carboxylate moieties were evaluated in vitro and by computational methods for their anti-diabetic potential to insight into their medicinal use for the management of type II diabetes mellitus. Interestingly all 14 compounds displayed high to significant inhibitory capability against the key carbohydrate's digestive enzyme α-glucosidase with IC50 values in range of 9.73-56.39 µM, as compared to marketed drug acarbose (IC50 = 873.34 ± 1.67 µM). Compounds 5i and 7c exhibited the highest inhibition, therefore, these two compounds were further evaluated for their mechanistic studies to explore its type of inhibition. Compounds 5i and 7c both displayed a concentration-dependent (competitive type of inhibition) with Ki values 7.14 ± 0.01, 6.15 ± 0.02 µM, respectively, which conclude their favourable interactions with the active site residues of the α-glucosidase. Interestingly all compounds are non-cytotoxic against BJ cell line. To further validate our findings, in-silico approaches like molecular docking, and molecular dynamic simulations were applied to investigate the mode of bindings of compounds with the enzyme and identifies their inhibition mechanism, which strongly complements our experimental findings.Communicated by Ramaswamy H. Sarma.

Identification of new pharmacophore against SARS-CoV-2 spike protein by multi-fold computational and biochemical techniques.

COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2's spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72-90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein's conformational arrangements. The binding free energy ΔGTOTAL of C3 (-38.0 ± 0.08 kcal/mol) and C6E (-41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2.

Efficient microwave synthesis of flurbiprofen derivatives and their enhancement of efficacy in chronic inflammatory pain models and gastro-protective potential in post-operative model.

Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives (NS5-NS8) were characterized by 1H NMR,13C NMR,19F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established in-vivo animal models. To evaluate post-operative and inflammatory pain, various doses of compounds [1, 3, 10, and 30 mg/kg (bwt)] were used, while their ulcerogenic potential was assessed at doses of 100 and 150 mg/kg (bwt). The incisional damage linked pain was significantly (p < 0.001) reduced by derivatives at different doses in both the acute and repeated tests with decreased response of phologistic agent-induced inflammation. The stomach histology and biochemical features demonstrate that the synthesized derivatives have no potential to cause ulcerogenicity as compared to aspirin and flurbiprofen. Furthermore, docking shows that the hydrazide moiety of these compounds is crucial in interacting within COX-2 binding site. Therefore, the synthesized compounds exhibit strong analgesic and anti-inflammatory effects and a low risk of causing ulcers. These attributes render them potentially valuable therapeutic agents for the treatment of pathological disorders associated with inflammation and pain.Communicated by Ramaswamy H. Sarma.

Meldrum-Based-1H-1,2,3-Triazoles as Antidiabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition Activity, Molecular Docking Studies, and In Silico Approach.

A series of novel alkyl derivatives (2-5a,b) and 1H-1,2,3-triazole analogues (7a-k) of Meldrum's acid were synthesized in a highly effective way by using "click" chemistry and screened for in vitro α-glucosidase inhibitory activity to examine their antidiabetic potential. 1H NMR, 13C-NMR, and high-resolution electrospray ionization mass spectra (HR-ESI-MS) were used to analyze each of the newly synthesized compounds. Interestingly, these compounds demonstrated high to moderate α-glucosidase inhibitory potency having an IC50 range of 4.63-80.21 µM. Among these derivatives, compound 7i showed extraordinary inhibitory activity and was discovered to be several times more potent than the parent compound Meldrum (1) and the standard drug acarbose. Later, molecular docking was performed to understand the binding mode and the binding strength of all the compounds with the target enzyme, which revealed that all compounds are well fitted in the active site of α-glucosidase. To further ascertain the structure of compounds, suitable X-ray single crystals of compounds 5a, 7a, and 7h were developed and studied. The current investigation has shown that combining 1H-1,2,3-triazole with the Meldrum moiety is beneficial. Furthermore, this is the first time that the aforementioned activity of these compounds has been reported.

Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies.

A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-ß-boswellic acid (ß-AKBA (1)) and 11-keto-ß-boswellic acid (ß-KBA (2)) was designed and synthesized by employing "click" chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between ß-AKBA-propargyl ester intermediate 3 or ß-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a-5k in the presence of copper iodide (CuI) and Hünig's base furnished the desired products-1H-1,2,3-triazole hybrids of ß-AKBA (6a-6k) and ß-KBA (7a-7k)-in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 µM. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.

Bio-oriented synthesis of ibuprofen derivatives for enhancement efficacy in post-operative and chronic inflammatory pain models.

The discovery of post-operative, chronic inflammatory pain and any gastroulcerogenic potential using well-established animal models in vivo with new structures, high efficiency, broad-spectrum, and low toxicity has been the focus of medicinal chemists. In the present article, we are reporting the design and synthesis of various derivatives of ibuprofen by modifying the carboxyl group of ibuprofen using three steps reactions; esterification under microwave-irradiation in 10 minutes, hydrazide formation, and finally schiff's base reaction. Microwave-assisted esterification reaction can be employed to quickly explore and increase molecular diversity in synthetic chemistry. All of the newly synthesized compounds (NS1-NS4) were characterized by 1H-, 13C-NMR, and HR-ESI-MS spectroscopy and evaluated for post-operative, chronic inflammatory pain and any gastroulcerogenic potential using well-established animal models in vivo. The synthesized compounds at the tested doses of 100 and 150 mg kg-1 significantly attenuated the incisional-injury induced post-operative pain like condition and, also inhibited the phologistic agent induced inflammatory responses in both the acute and chronic testing paradigms. The gastric histological and biochemical parameters exhibited that the synthesized compounds were devoid of any ulcerogenic potential in comparison to aspirin and ibuprofen. These findings concluded that the synthesized ibuprofen derivatives exhibited profound analgesic, anti-inflammatory properties with reduced ulcerogenic potential and might be considered as effective therapeutic agents to treat pathological conditions associated with pain and inflammation.

Biochemical and in silico inhibition of bovine and human carbonic anhydrase-II by 1H-1,2,3-triazole analogs.

A series of 1H-1,2,3-triazole analogs (7a-7d and 9a-9s) were synthesized via "click" chemistry and evaluated for in vitro carbonic anhydrase-II (bovine and human) inhibitory activity. The synthesis of intermediates, 7a and 7c, was achieved by using (S)-(-)ethyl lactate as a starting material. These compounds (7a and 7c) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in 1,4-dioxane, reflux at 90-120°C for 8 h using Pd(PPh3)4 as a catalyst (5 mol%), and K2CO3 (3.0 equiv)/K2PO4 (3.0 equiv) as a base to produce target 1H-1,2,3-triazole molecules (9a-9s) for a good yield of 67-86%. All the synthesized compounds were characterized through NMR spectroscopic techniques. Furthermore, all those compounds have shown significant inhibitory potential for both sources of carbonic anhydrase-II (CA-II). In the case of bCA-II, compounds 9i, 7d, 9h, 9o, 9g, and 9e showed potent activity with IC50 values in the range of 11.1-17.8 µM. Whereas for hCA-II, compounds 9i, 9c, 9o, and 9j showed great potential with IC50 values in the range of 10.9-18.5 µM. The preliminary structure-activity relationship indicates that the presence of the 1H-1,2,3-triazole moiety in those synthesized 1H-1,2,3-triazole analogs (7a-7d and 9a-9s) significantly contributes to the overall activity. However, several substitutions on this scaffold affect the activity to several folds. The selectivity index showed that compounds 9c, 9k, and 9p are selective inhibitors of hCA-II. Kinetics studies showed that these compounds inhibited both enzymes (bCA-II and hCA-II) in a competitive manner. Molecular docking indicates that all the active compounds fit well in the active site of CA-II. This study has explored the role of 1H-1,2,3-triazole-containing compounds in the inhibition of CA-II to combat CA-II-related disorders.

Synthesis and antidepressant-like effects of new 5-epi-incensole and 5-epi- incensole acetate in chronic unpredictable mild stress model of depression; behavioural and biochemical correlates.

In the current investigation, 5-epi-incensole (3) and 5-epi-incensole acetate (5) were synthesized from the most potent anti-depressant constituents incensole (1) and incensole acetate (2) of Boswellia papyrifera Hochst. The resulting compounds were evaluated for their ability to ameliorate depressive symptoms in forced swim test (FST) and tail suspension test (TST) in chronic unpredictable mild stress (CUMS) induced depression paradigm. The results demonstrated that compounds 3 and 5 at the doses of 1 and 3 mg/kg administered for 28 days, significantly reduced the immobility time in FST and TST and were devoid of any effect on locomotor activity in the open field test (OFT). Both compounds 3 and 5 also reversed CUMS-induced reduction in the weight of animals and aversion in sucrose preference. The tested compounds also inhibited Monoamine oxidase-A (MAO) enzyme and increased the levels of brain noradrenaline (NA) and 5-Hydroxytryptamine (5-HT), decreased plasma corticosterone and pro-inflammatory cytokines including TNF-α, IL-6 in hippocampal homogenates. Compounds 3 and 5 also significantly reduced the increased lipid peroxidation and nitrite levels; decreased glutathione levels, and catalase activities in mice undergoing CUMS protocol. The binding mode of compounds 3 and 5 was predicted at the monoamine oxidase substrate binding site by molecular docking having docking scores of > -6 kcal/mol. Taken together these data revealed that compounds 3 and 5 exerted antidepressant-like effects in chronic unpredictable mild stress-induced depression paradigm and are likely mediated via modulating the central oxidative stress, MAO-A activity with a consequent increase in brain NA and 5-HT levels in inflammatory pathways.

Virtual 2D map of cyanobacterial proteomes.

Cyanobacteria are prokaryotic Gram-negative organisms prevalent in nearly all habitats. A detailed proteomics study of Cyanobacteria has not been conducted despite extensive study of their genome sequences. Therefore, we conducted a proteome-wide analysis of the Cyanobacteria proteome and found Calothrix desertica as the largest (680331.825 kDa) and Candidatus synechococcus spongiarum as the smallest (42726.77 kDa) proteome of the cyanobacterial kingdom. A Cyanobacterial proteome encodes 312.018 amino acids per protein, with a molecular weight of 182173.1324 kDa per proteome. The isoelectric point (pI) of the Cyanobacterial proteome ranges from 2.13 to 13.32. It was found that the Cyanobacterial proteome encodes a greater number of acidic-pI proteins, and their average pI is 6.437. The proteins with higher pI are likely to contain repetitive amino acids. A virtual 2D map of Cyanobacterial proteome showed a bimodal distribution of molecular weight and pI. Several proteins within the Cyanobacterial proteome were found to encode Selenocysteine (Sec) amino acid, while Pyrrolysine amino acids were not detected. The study can enable us to generate a high-resolution cell map to monitor proteomic dynamics. Through this computational analysis, we can gain a better understanding of the bias in codon usage by analyzing the amino acid composition of the Cyanobacterial proteome.

Exploring Dose-Dependent Cytotoxicity Profile of Gracilaria edulis-Mediated Green Synthesized Silver Nanoparticles against MDA-MB-231 Breast Carcinoma.

Green-based synthesis of metal nanoparticles using marine seaweeds is a rapidly growing technology that is finding a variety of new applications. In the present study, the aqueous extract of a marine seaweed, Gracilaria edulis, was employed for the synthesis of metallic nanoparticles without using any reducing and stabilizing chemical agents. The visual color change and validation through UV-Vis spectroscopy provided an initial confirmation regarding the Gracilaria edulis-mediated green synthesized silver nanoparticles. The dynamic light scattering studies and high-resolution transmission electron microscopy pictographs exhibited that the synthesized Gracilaria edulis-derived silver nanoparticles were roughly spherical in shape having an average size of 62.72 ± 0.25 nm and surface zeta potential of -15.6 ± 6.73 mV. The structural motifs and chemically functional groups associated with the Gracilaria edulis-derived silver nanoparticles were observed through X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy. Further, the synthesized nanoparticles were further screened for their antioxidant properties through DPPH, hydroxyl radical, ABTS, and nitric oxide radical scavenging assays. The phycosynthesized nanoparticles exhibited dose-dependent cytotoxicity against MDA-MB-231 breast carcinoma cells having IC50 value of 344.27 ± 2.56 µg/mL. Additionally, the nanoparticles also exhibited zone of inhibition against pathogenic strains of Bacillus licheniformis (MTCC 7425), Salmonella typhimurium (MTCC 3216), Vibrio cholerae (MTCC 3904), Escherichia coli (MTCC 1098), Staphylococcus epidermidis (MTCC 3615), and Shigella dysenteriae (MTCC9543). Hence, this investigation explores the reducing and stabilizing capabilities of marine sea weed Gracilaria edulis for synthesizing silver nanoparticles in a cost-effective approach with potential anticancer and antimicrobial activity. The nanoparticles synthesized through green method may be explored for their potential utility in food preservative film industry, biomedical, and pharmaceutical industries.

Edible Mushrooms as Novel Myco-Therapeutics: Effects on Lipid Level, Obesity and BMI.

Obesity, usually indicated by a body mass index of more than 30 kg/m2, is a worsening global health issue. It leads to chronic diseases, including type II diabetes, hypertension, and cardiovascular diseases. Conventional treatments for obesity include physical activity and maintaining a negative energy balance. However, physical activity alone cannot determine body weight as several other factors play a role in the overall energy balance. Alternatively, weight loss may be achieved by medication and surgery. However, these options can be expensive or have side effects. Therefore, dietary factors, including dietary modifications, nutraceutical preparations, and functional foods have been investigated recently. For example, edible mushrooms have beneficial effects on human health. Polysaccharides (essentially ß-D-glucans), chitinous substances, heteroglycans, proteoglycans, peptidoglycans, alkaloids, lactones, lectins, alkaloids, flavonoids, steroids, terpenoids, terpenes, phenols, nucleotides, glycoproteins, proteins, amino acids, antimicrobials, and minerals are the major bioactive compounds in these mushrooms. These bioactive compounds have chemo-preventive, anti-obesity, anti-diabetic, cardioprotective, and neuroprotective properties. Consumption of edible mushrooms reduces plasma triglyceride, total cholesterol, low-density lipoprotein, and plasma glucose levels. Polysaccharides from edible mushrooms suppress mRNA expression in 3T3-L1 adipocytes, contributing to their anti-obesity properties. Therefore, edible mushrooms or their active ingredients may help prevent obesity and other chronic ailments.

Exploring the Bioactive Potentials of C60-AgNPs Nano-Composites against Malignancies and Microbial Infections.

At present, the potential role of the AgNPs/endo-fullerene molecule metal nano-composite has been evaluated over the biosystems in-vitro. The intra-atomic configuration of the fullerene molecule (C60) has been studied in-vitro for the anti-proliferative activity of human breast adenocarcinoma (MDA-MB-231) cell lines and antimicrobial activity against a few human pathogens that have been augmented with the pristine surface plasmonic electrons and antibiotic activity of AgNPs. Furthermore, FTIR revealed the basic vibrational signatures at ~3300 cm-1, 1023 cm-1, 1400 cm-1 for O-H, C-O, and C-H groups, respectively, for the carbon and oxygen atoms of the C60 molecule. NMR studies exhibited the different footprints and magnetic moments at ~7.285 ppm, explaining the unique underlying electrochemical attributes of the fullerene molecule. Such unique electronic and physico-chemical properties of the caged carbon structure raise hope for applications into the drug delivery domain. The in-vitro dose-dependent application of C60 elicits a toxic response against both the breast adenocarcinoma cell lines and pathogenic microbes. That enables the use of AgNPs decorated C60 endo fullerene molecules to design an effective anti-cancerous drug delivery and antimicrobial agent in the future, bringing a revolutionary change in the perspective of a treatment regime.

Nanotechnology in combating biofilm: A smart and promising therapeutic strategy.

Since the birth of civilization, people have recognized that infectious microbes cause serious and often fatal diseases in humans. One of the most dangerous characteristics of microorganisms is their propensity to form biofilms. It is linked to the development of long-lasting infections and more severe illness. An obstacle to eliminating such intricate structures is their resistance to the drugs now utilized in clinical practice (biofilms). Finding new compounds with anti-biofilm effect is, thus, essential. Infections caused by bacterial biofilms are something that nanotechnology has lately shown promise in treating. More and more studies are being conducted to determine whether nanoparticles (NPs) are useful in the fight against bacterial infections. While there have been a small number of clinical trials, there have been several in vitro outcomes examining the effects of antimicrobial NPs. Nanotechnology provides secure delivery platforms for targeted treatments to combat the wide range of microbial infections caused by biofilms. The increase in pharmaceuticals' bioactive potential is one of the many ways in which nanotechnology has been applied to drug delivery. The current research details the utilization of several nanoparticles in the targeted medication delivery strategy for managing microbial biofilms, including metal and metal oxide nanoparticles, liposomes, micro-, and nanoemulsions, solid lipid nanoparticles, and polymeric nanoparticles. Our understanding of how these nanosystems aid in the fight against biofilms has been expanded through their use.

Heterogeneous Pd/C-catalyzed, ligand free Suzuki-Miyaura coupling reaction furnishes new p-terphenyl derivatives.

A series of new para-terphenyls derivatives have been efficiently synthesized by a ligand-free heterogeneous Pd/C-catalyzed two-fold Suzuki-Miyaura coupling reaction. Methyl 5-bromo-2-iodobenzoate was selected to react with a variety of different aryl boronic acids (2a-i). Nine new p-terphenyl derivatives (3a-i) were prepared and the structures were confirmed by several analytical techniques including infrared, spectroscopy, 1H and 13C NMR spectroscopy, mass spectrometry, and in the case of compound 3 b, by X-ray diffraction method. The new derivatives were obtained in very good yields (78-91%). This synthetic facile route is envisioned to improve the preparation of p-terphenyl-based natural products.

Naturally Occurring O-Heterocycles as Anticancer Agents.

Cancer is a leading cause of death worldwide. Proper efficient drugs are required to treat this deadly disease. Natural products have long been a vital source of anticancer agents and they have generated various "lead compounds" suitable for drug developments. With the recent advancement of chemical synthesis and bioevaluation techniques, these lead compounds of natural origins have been utilized for the production of useful anticancer drugs. Among the naturally occurring bioactive compounds, various O-heterocycles have been evaluated as remarkable cancer therapeutic agents. These compounds generally possess unique structures and novel mechanisms of action. In the present review article, some selected O-heterocycles as promoting anticancer agents have been discussed in brief. Various natural sources and chemistry, as well as bioactivities of these compounds, have been described. The development of improved analogues of these compounds through synthetic modifications and efficient bioevaluation, along with proper studies on structure-activity relationship and mechanism of actions, has been mentioned. The article has demonstrated the recent relevance of naturally occurring O-heterocyclic compounds in the current anticancer drug discovery and development scenario.

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole.

Herein, a series of novel 1H-1,2,3-triazole and carboxylate derivatives of metronidazole (5a-i and 7a-e) were synthesized and evaluated for their antimicrobial activity in vitro. All the newly synthesized compounds were characterized by 1H NMR, 13C NMR, HRMS, and 19F NMR (5b, 5c and 5h) spectroscopy wherever applicable. The structures of compounds 3, 5c and 7b were unambiguously confirmed by single crystal X-ray analysis diffraction method. Single crystal X-ray structure analysis supported the formation of the metronidazole derivatives. The antimicrobial (antifungal and antibacterial) activity of the prepared compounds was studied. All compounds (except 2 and 3) showed a potent inhibition rate of fungal growth as compared to control and metronidazole. The synthetic compounds also showed higher bacterial growth inhibiting effects compared to the activity of the parent compound. Amongst the tested compounds 5b, 5c, 5e, 7b and 7e displayed excellent potent antimicrobial activity. The current study has demonstrated the usefulness of the 1H-1,2,3-triazole moiety in the metronidazole skeleton.

Cembranoids from Boswellia species.

Frankincense of Boswellia species has long been used in traditional medicines, mainly for its interesting anti-inflammatory and anti-depressant properties of its di- and triterpenes. Boswellic acids (triterpenes) and cembranoids (diterpenes) are the major constituents of frankincense from all reported species which are responsible for the overall biological activity of frankincense. Boswellic acids have been thoroughly investigated for decades but cembranoids have attracted considerable attention only recently, and a good number of publications have highlighted the important role of these 14-membered rings in contributing to the superior anti-inflammatory activity of the sacred resin. Partial and total syntheses of some cembranoids from frankincense have been reported. Their therapeutic potential is not limited to the well proven anti-inflammatory activity but also to their recently reported anti-depressant properties. There is a considerable number of publications in the field of cembranoids of Boswellia species where we feel a review in this topic will be of interest to the readership of Phytochemistry. In this article we have discussed the chemistry (isolation and chemical structures as well as synthetic studies), biogenesis and bioactivity of the reported cembranoids of Boswellia species. The structural discrepancies due to wrongly assigned structures of some cembranoids have been highlighted and corrected. We have covered the related literature up to the end of 2020.

Synthesis of New 1H-1,2,3-Triazole Analogs in Aqueous Medium via "Click" Chemistry: A Novel Class of Potential Carbonic Anhydrase-II Inhibitors.

A series of novel 1H-1,2,3-triazole analogs (9a-j) were synthesized via "Click" chemistry and Suzuki-Miyaura cross-coupling reaction in aqueous medium. The compounds were evaluated for their carbonic anhydrase-II enzyme inhibitory activity in vitro. The synthesis of triazole 7a was accomplished using (S)-(-) ethyl lactate as a starting material. This compound (7a) underwent Suzuki-Miyaura cross-coupling reaction with different arylboronic acids in aqueous medium to afford the target molecules, 9a-j in good yields. All newly synthesized compounds were characterized by 1H NMR, 13C NMR, FT-IR, HRMS, and where applicable 19F NMR spectroscopy (9b, 9e, 9h, and 9j). The new compounds have shown moderate inhibition potential against carbonic anhydrase-II enzyme. A preliminary structure-activity relationship suggested that the presence of polar group at the 1H-1,2,3-triazole substituted phenyl ring in these derivatives (9a-j) has contributed to the overall activity of these compounds. Furthermore, via molecular docking, it was deduced that the compounds exhibit inhibitory potential through direct binding with the active site residues of carbonic anhydrase-II enzyme. This study has unraveled a new series of triazole derivatives as good inhibitors against carbonic anhydrase-II.

Recent Advances in the Stereoselective Total Synthesis of Natural Pyranones Having Long Side Chains.

Pyranone natural products have attracted great attention in recent years from chemists and biologists due to their fascinating stereoisomeric structural features and impressive bioactivities. A large number of stereoselective total syntheses of these compounds have been described in the literature. The natural pyranones with long side chains have recently received significant importance in the synthetic field. In the present article, we aim to review the modern progress of the stereoselective total syntheses of these natural pyranones containing long-chain substituents.

Synthesis of novel (R)-4-fluorophenyl-1H-1,2,3-triazoles: A new class of α-glucosidase inhibitors.

Diabetes is a non-communicable disease, which occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicates an increase in the trend of people diagnosed with Type 2 diabetes mellitus (T2DM). α-Glucosidase inhibitors are known to reduce the impact of carbohydrates on blood glucose level and prevent the digestion of carbohydrates. α-glucosidase inhibitors hold great potential for the treatment of T2DM. In search of better α-glucosidase inhibitors, a series of novel (R)-4-fluorophenyl-1H-1,2,3-triazole derivatives were synthesized (6 and 8a-n) and evaluated for their α-glucosidase inhibitory activity in vitro. All new compounds were characterized by 1H NMR, 13C NMR, 19F NMR, ESI-MS, and where applicable by single crystal X-ray diffraction (8 m). A preliminary structure-activity relationship suggested that the presence of 1H-1,2,3-triazole ring in (R)-4-fluorophenyl-1H-1,2,3-triazole derivatives has remarkable contribution in the overall activity. Molecular docking studies were carried out to investigate the binding mode of compounds within the active site of the α-glucosidase enzyme. Docking results are in complete agreement with the experimental finding. This study unravelled a new class of triazole derivatives with α-glucosidase inhibitory activity.