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This study deals with the synthesis of benzophenone sulfonamides hybrids (1–31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-nitrobenzenesulfonohydrazide), 2 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-3′′-nitrobenzenesulfonohydrazide), 3 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-methoxybenzenesulfonohydrazide), 4 (3′′,5′′-dichloro-2′′-hydroxy-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2′′,4′′-dichloro-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)-N′-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2′′-chloro-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC50 value in the range of 3.90–17.99 µM. These compounds showed superior activity than standard acetohydroxamic acid (IC50 = 29.20 ± 1.01 µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by 1H NMR, 13C NMR, EI-MS and FAB-MS spectroscopic techniques.

Background:Inflammation is a biological rejoinder of vascular tissues against destructive agents e.g. irritants, damaged cell or pathogens. During inflammation, respiratory burst occurs by activated phagocytes which help to destroy invading pathogens. Phagocytic cells such as neutrophils and macrophages are one of the major sources of reactive oxygen species (ROS) and nitric oxide (NO). Normally, the redox environment is maintained by various antioxidant defense systems, however, these reactive oxygen species may be destructive and can lead to various pathological conditions.Methods:Benzophenone esters and sulfonates (1-18) were synthesized through one pot synthesis by reacting 4-hydroxy benzophenone either different benzoyl chloride or sulfonyl chloride. These synthetic compounds were evaluated for their in vitro immunosuppressive potential on two parameters of innate immune response including inhibition of intracellular reactive oxygen species (ROS) and nitric oxide (NO). ROS were induced in polymorphonuclear leukocytes (PMNs) isolated from human whole blood by serum opsonized zymosan stimulation, whereas NO were produced in J774.2 cells by lipopolysachharides (LPS) stimulation. Moreover, cytotoxicity of compounds was also determined using NIH-3T3 fibroblast cells (ATCC, Manassas, USA) was evaluated by using the standard MTT colorimetric assay.Results:All compounds inhibited the production of ROS at various extent among which compounds 2, 5, 6, 8, 10, 13 and 16 were found to be the potent inhibitors of ROS with IC50 values ranging between (1.0 - 2.2 µg/mL) as compared to ibuprofen (IC50 = 2.5 ± 0.6 µg/mL) as the standard drug. Compounds 2, 7, 11, 13, 14 and 18 showed good inhibition of NO production with % inhibition values ranging between (63.6% - 76.7%) at concentration of 25 µg/mL as compared to NG-monomethyl-Larginine (L-NMMA 65.6 ± 1.1 µg/mL) as the standard. All other derivatives showed moderate to low level of inhibition on both tested parameters. Cytotoxicity activity also showed nontoxicity of synthetic compounds. Structures of all the synthetic compounds were confirmed through 1H-NMR, 13C-NMR, EI-MS and HREI-MS spectroscopic techniques.Conclusion:Compounds 2 and 13 were found to be good dual antiinflammatory (ROS and NO) agent. However, compounds 5, 6, 8, 10 and 16 were found to be selectively active for ROS inhibitory studies. Compounds 7, 11, 14 and 18 were discriminatory active at NO inhibition assay. These initial findings of antiinflammatory activity concluded that these compounds might have the potential to develop a novel non-steroidal antiinflammatory drugs (NSAIDs), non-acidic antiinflammatory agent. Most active compounds 2, 5-8, 10, 13, 14 and 16 showed nontoxicity of synthetic compounds.

Benzohydrazide derivatives 1–43 were synthesized via “one-pot” reaction and structural characterization of these synthetic derivatives was carried out by different spectroscopic techniques such as 1H NMR and EI-MS. The synthetic molecules were evaluated for their in vitro urease inhibitory activity. All synthetic derivatives showed good inhibitory activities in the range of (IC50 = 0.87 ± 0.31–19.0 ± 0.25 µM) as compared to the standard thiourea (IC50 = 21.25 ± 0.15 µM), except seven compounds 17, 18, 23, 24, 29, 30, and 41 which were found to be inactive. The most active compound of the series was compound 36 (IC50 = 0.87 ± 0.31 μM) having two chloro groups at meta positions of ring A and methoxy group at para position of ring B. The structure–activity relationship (SAR) of the active compounds was established on the basis of different substituents and their positions in the molecules. Kinetic studies of the active compounds revealed that compounds can inhibit enzyme via competitive and noncompetitive modes. In silico study was also performed to understand the binding interactions of the molecules (ligand) with the active site of enzyme.

Novel derivatives of flurbiprofen 1–18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2–9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11–15, and benzyl substituted 2-mercapto oxadiazole derivatives 16–18 were synthesized and characterized by EI-MS, 1H and 13C NMR spectroscopic techniques. All derivatives 1–18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC50 = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC50 = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC50 = 1.69 ± 0.1 µM), 3 (IC50 = 1.04 ± 0.3 µM), 9 (IC50 = 1.25 ± 1.05 µM), and 13 (IC50 = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme.

Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3–29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.

Photosynthesis can be probed through Chlorophyll a fluorescence induction (FI), which provides detailed insight into the electron transfer process in Photosystem II, and beyond. Here, we have systematically studied the natural variation of the fast phase of the FI, i.e. the OJIP phase, in rice. The OJIP phase of the Chl a fluorescence induction curve is referred to as "fast transient" lasting for less than a second; it is obtained after a dark-adapted sample is exposed to saturating light. In the OJIP curve, "O" stands for "origin" (minimal fluorescence), "P" for "peak" (maximum fluorescence), and J and I for inflection points between the O and P levels. Further, Fo is the fluorescence intensity at the "O" level, whereas Fm is the intensity at the P level, and Fv (= Fm - Fo) is the variable fluorescence. We surveyed a set of quantitative parameters derived from the FI curves of 199 rice accessions, grown under both field condition (FC) and growth room condition (GC). Our results show a significant variation between Japonica (JAP) and Indica (IND) subgroups, under both the growth conditions, in almost all the parameters derived from the OJIP curves. The ratio of the variable to the maximum (Fv/Fm) and of the variable to the minimum (Fv/Fo) fluorescence, the performance index (PIabs), as well as the amplitude of the I-P phase (AI-P) show higher values in JAP compared to that in the IND subpopulation. In contrast, the amplitude of the O-J phase (AO-J) and the normalized area above the OJIP curve (Sm) show an opposite trend. The performed genetic analysis shows that plants grown under GC appear much more affected by environmental factors than those grown in the field. We further conducted a genome-wide association study (GWAS) using 11 parameters derived from plants grown in the field. In total, 596 non-unique significant loci based on these parameters were identified by GWAS. Several photosynthesis-related proteins were identified to be associated with different OJIP parameters. We found that traits with high correlation are usually associated with similar genomic regions. Specifically, the thermal phase of FI, which includes the amplitudes of the J-I and I-P subphases (AJ-I and AI-P) of the OJIP curve, is, in turn, associated with certain common genomic regions. Our study is the first one dealing with the natural variations in rice, with the aim to characterize potential candidate genes controlling the magnitude and half-time of each of the phases in the OJIP FI curve.

(E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1–27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α-amylase and α-glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14–17, 19, and 21–25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC50 values ranging (IC50 = 13.02 ± 0.04–46.90 ± 0.05 µM) and (IC50 = 13.09 ± 0.08–46.44 ± 0.24 µM) in comparison to standard acarbose (IC50 = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α-amylase and α-glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α-amylase and α-glucosidase inhibitors 5, 7, 9, 15, 24, and 27, suggested non-competitive and competitive types of inhibition mechanism for α-amylase and α-glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H

Identifying new options to improve photosynthetic capacity is a major approach to improve crop yield potential. Here we report that overexpression of the gene encoding the transcription factor mEmBP-1 led to simultaneously increased expression of many genes in photosynthesis, including genes encoding Chl a,b-binding proteins (Lhca and Lhcb), PSII (PsbR3 and PsbW) and PSI reaction center subunits (PsaK and PsaN), chloroplast ATP synthase subunit, electron transport reaction components (Fd1 and PC), and also major genes in the Calvin–Benson–Bassham cycle, including those encoding Rubisco, glyceraldehyde phosphate dehydrogenase, fructose bisphosphate aldolase, transketolase, and phosphoribulokinase. These increased expression of photosynthesis genes resulted in increased leaf chlorophyll pigment, photosynthetic rate, biomass growth, and grain yield both in the greenhouse and in the field. Using EMSA experiments, we showed that mEmBP-1a protein can directly bind to the promoter region of photosynthesis genes, suggesting that the direct binding of mEmBP-1a to the G-box domain of photosynthetic genes up-regulates expression of these genes. Altogether, our results show that mEmBP-1a is a major regulator of photosynthesis, which can be used to increase rice photosynthesis and yield in the field.

Non-photochemical quenching (NPQ) of the excited state of chlorophyll a is a major photoprotective mechanism plants utilize to survive under high light. Here, we report the impact of long-term light quality treatment on photosynthetic properties, especially NPQ in rice. We used three LED-based light regimes, i.e., red (648–672 nm), blue (438–460 nm), and “warm” white light (529–624 nm), with the incident photon flux density of 300 µmol photons m−2 s−1, the difference in the absorbed photon flux densities by leaves grown under different light quality being less than 7%. Our results show that blue light, as compared to white light, induced a significant decrease in Fv/Fm, a decreased rate of reduction of P700+ after P700 was completely oxidized; furthermore, blue light also induced higher NPQ with an increased initial speed of NPQ induction, which corresponds to the qE component of NPQ, and a lower maximum quantum yield of PSII, i.e., Y(II). In contrast, rice grown under long-term red light showed decreased Y(II) and increased NPQ, but with no change in Fv/Fm. Furthermore, we found that rice grown under either blue or red light showed decreased transcript abundance of both catalase and ascorbate peroxidase, together with an increased H2O2 content, as compared to rice grown under white light. All these data suggest that even under a moderate incident light level, rice grown under blue or red light led to compromised antioxidant system, which contributed to decreased quantum yield of photosystem II and increased NPQ.

BACKGROUND Glucuronidation is essential for the metabolism and excretion of toxic substances. β-Glucuronidase enzyme slows down the process of glucuronidation, and thus plays an important role in the on-set of colorectal carcinoma, and many other diseases. Inhibition of β- glucuronidase activity is thus identified as an important approach for the treatment of several diseases. OBJECTIVE Current study was aimed to synthesize a library of 2-oxo-1,2,3,4-tetrahydropyrimidine and to evaluate their β-glucuronidase inhibitory activity, and their mode of enzyme inhibition. METHOD We synthesized a series of 2-oxo-1,2,3,4-tetrahydropyrimidines 1-25 by fusing urea, ethyl acetoacetate, and a variety of aldehydes using copper nitrate trihydrate as catalyst. All synthesized compounds were evaluated for their in vitro β-glucuronidase inhibitory activity. In addition, molecular docking studies were also performed by using MOE docking tools. RESULTS Eighteen compounds showed inhibitory activity better than the standard D-saccharic acid 1,4-lactone, a well known β-glucuronidase inhibitor (IC50 = 45.75 ± 2.16 µM). Compound 20 (IC50 = 1.36 ± 0.03 µM) showed an excellent inhibitory activity, thirty-five folds superior to the standard. Docking results highlighted the role of various chemical moieties at different positions on 2- oxo-1,2,3,4-tetrahydropyrimidine skeleton in enzyme inhibitory activity. CONCLUSION This study has identified a class of potent β-glucuronidase inhibitors with the potential to be investigated further.

Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3–27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1H-, and 13C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC50 values of 1.21–51.42 μM as compared to the standard thiourea (IC50 = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1–5, 7, 8, 10, 12, 14–18, 20–22, 24–27 were found to be more active showing IC50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study.

Thirty-three 4-amino-1,2,4-triazole derivatives 1–33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via 1H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1–33 exhibited good to moderate in vitro α-amylase and α-glucosidase inhibitory activities in the range of IC50 values 2.01 ± 0.03–6.44 ± 0.16 and 2.09 ± 0.08–6.54 ± 0.10 µM as compared to the standard acarbose (IC50 = 1.92 ± 0.17 µM) and (IC50 = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1–33 followed mixed and non-competitive type of inhibitions against α-amylase and α-glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies.

Thirty benzofuran-2-yl(phenyl)methanones 1–30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K2CO3 in acetonitrile at room temperature to afford the desired benzofurans 1–30. All compounds were screened for their in vitro α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC50 values ranges for α-amylase inhibition (IC50 = 18.04–48.33 µM), DPPH (IC50 = 16.04–32.33 µM) and ABTS (IC50 = 16.99–33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC50 = 16.08 ± 0.07 µM) for α-amylase, ascorbic acid (IC50 = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein–ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18–20, 22, and 25–30 were structurally new.

Twenty-five derivatives of 5-chloro-2-aryl benzo[d]thiazole (1–25) were synthesized and evaluated for their α-glucosidase (S. cerevisiae EC 3.2.1.20) inhibitory activity in vitro. Among them eight compounds showed potent activity with IC50 values between 22.1 ± 0.9 and 136.2 ± 5.7 μM, when compared with standard acarbose (IC50 = 840 ± 1.73 μM). The most potent compounds 4, 9, and 10 showed IC50 values in the range of 22.1 ± 0.9 to 25.6 ± 1.5 μM. Compounds 2, 5, 11, and 19 showed IC50 values within the range of 40.2 ± 0.5 to 60.9 ± 2.0 μM. Compounds 1 and 3 were also found to be good inhibitors with IC50 values 136.2 ± 5.7 and 104.8 ± 9.9 μM, respectively. Their activities were compared with α-glucosidase inhibitor drug acarbose (standard) (IC50 = 840 ± 1.73 μM). The remaining compounds were inactive. Structure-activity relationships (SAR) have also been established. Kinetics studies indicated compounds 2, 3, 10, 19, and 25 to be non-competitive, while 1, 5, 9, and 11 as competitive inhibitors of α-glucosidase enzyme. All the active compounds (1–5, 9–11, and 19) were also found to be non-cytotoxic, in comparison to the standard drug i.e., doxorubicin (IC50 = 0.80 ± 0.12 μM) in MTT assay. Furthermore, molecular interactions of active compounds with the enzyme binding sites were predicted through molecular modeling studies.

A series of benzoxazinones 1 – 28 were synthesized via reaction of anthranilic acid with various substituted benzoyl chlorides in the presence of triethylamine in chloroform. Compounds 1 – 18 showed a good inhibition of α -chymotrypsin with IC 50 ± SEM values between 6.5 and 341.1 μM. Preliminary structure-activity relationships studies indicated that the presence of substituents on benzene ring reduces the inhibitory potential of benzoxazinone. Also the increased inhibitory potential due to fluoro group at phenyl substituent was observed followed by chloro and bromo substituents. Compounds with strong electron donating or withdrawing groups on phenyl substituent, showed a good inhibitory potential at ortho > meta > para position. Kinetics studies showed diverse types of inhibition, except uncompetitive-type inhibition. The Ki values ranged between 4.7 and 341.2 μM. Interestingly, most of these compounds were non-cytotoxic to 3T3 cell line at 30 μM, except compounds 6 , 14 and 15 . Competitive inhibitors of chymotrypsin are like to inhibit other α -chymotrypsin-like serine proteases due to structural and functional similarities between them. The inhibitors identified during the current study deserve to be further studied for their therapeutic potential against abnormalities mediated by chymotrypsin or other serine protease.

Coumarin sulfonates 4-43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC50=54.2±9.2μM). Eleven compounds 6 (IC50=46.60±14.6μM), 8 (IC50=11.50±6.5μM), 15 (IC50=21.40±12.2μM), 19 (IC50=5.75±0.86μM), 22 (IC50=10.27±1.06μM), 23 (IC50=33.09±5.61μM), 24 (IC50=4.93±0.58μM), 25 (IC50=21.96±14.74μM), 29 (IC50=12.47±9.2μM), 35 (IC50=20.20±13.4μM) and 37 (IC50=14.47±5.02μM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4-43 were characterized by different available spectroscopic techniques such as 1H NMR, 13C NMR, EIMS and HRMS. CHN analysis was also performed.

© 2019 Elsevier Inc. The current study is concerned with the identification of lead molecules based on the bis-coumarin scaffold having selective urease inhibitory and antiglycation activities. For that purpose, bis-coumarins (1-44) were synthesized and structurally characterized by different spectroscopic techniques. Eight derivatives 4, 8-10, 14, 17, 34, and 40 demonstrated urease inhibition in the range of IC50 = 4.4 ± 0.21–115.6 ± 2.13 μM, as compared to standard thiourea (IC50 = 21.3 ± 1.3 μM). Especially, compound 17 (IC50 = 4.4 ± 0.21 μM) was found to be five-fold more potent than the standard. Kinetic studies were also performed on compound 17 in order to identify the mechanism of inhibition. Kinetic studies revealed that compound 17 is a competitive inhibitor. Antiglycation activity was evaluated using glycation of bovine serum albumin by methylglyoxal in vitro. Compounds 2, 11-13, 16, 17, 19–22, 35, 37, and 42 showed good to moderate antiglycation activities with IC50 values of 333.63–919.72 μM, as compared to the standard rutin (IC50 = 294.46 ± 1.5 μM). Results of both assays showed that the compounds with urease inhibitory activity did not show any antiglycation potential, and vice versa. Only compound 17 showed dual inhibition potential. All compounds were also evaluated for cytotoxicity. Compounds 17, 19, and 37 showed a weak toxicity towards 3 T3 mouse fibroblast cell line. All other compounds were found to be non-cytotoxic. Urease inhibition is an approach to treat infections caused by ureolytic bacteria whereas inhibition of glycation of proteins is a strategy to avoid late diabetic complications. Therefore, these compounds may serve as leads for further research.

Dihydropyrimidones 1-37 were synthesized via a 'one-pot' three component reaction according to well-known Biginelli reaction by utilizing Cu(NO3)2·3H2O as catalyst, and screened for their in vitro β-glucuronidase inhibitory activity. It is worth mentioning that amongst the active molecules, compounds 8 (IC50=28.16±.056μM), 9 (IC50=18.16±0.41μM), 10 (IC50=22.14±0.43μM), 13 (IC50=34.16±0.65μM), 14 (IC50=17.60±0.35μM), 15 (IC50=15.19±0.30μM), 16 (IC50=27.16±0.48μM), 17 (IC50=48.16±1.06μM), 22 (IC50=40.16±0.85μM), 23 (IC50=44.16±0.86μM), 24 (IC50=47.16±0.92μM), 25 (IC50=18.19±0.34μM), 26 (IC50=33.14±0.68μM), 27 (IC50=44.16±0.94μM), 28 (IC50=24.16±0.50μM), 29 (IC50=34.24±0.47μM), 31 (IC50=14.11±0.21μM) and 32 (IC50=9.38±0.15μM) found to be more potent than the standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Molecular docking study was conducted to establish the structure-activity relationship (SAR) which demonstrated that a number of structural features of dihydropyrimidone derivatives were involved to exhibit the inhibitory potential. All compounds were characterized by spectroscopic techniques such as (1)H, (13)C NMR, EIMS and HREI-MS.

Inhibition of α-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[2,3-c] pyrazoles (1-35) were synthesized and evaluated for their α-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast α-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (Ki=9.75±0.07, 46±0.0001, and 69.16±0.01μM, respectively), compound 22 is a competitive inhibitor (Ki=190±0.016μM), while 33 was an uncompetitive inhibitor (Ki=45±0.0014μM) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed. This study identifies non-cytotoxic novel inhibitors of α-glucosidase enzyme for further investigation as anti-diabetic agents.

One of the most prevailing metabolic disorder diabetes mellitus has become the global health issue that has to be addressed and cured. Different marketed drugs have been made available for the treatment of diabetes but there is still a need of introducing new therapeutic agents that are economical and have lesser or no side effects. The current study deals with the synthesis of indole acrylonitriles (3–23) and the evaluation of these compounds for their potential for α-glucosidase inhibition. The structures of these synthetic molecules were deduced by using different spectroscopic techniques. Acarbose (IC50 = 2.91 ± 0.02 μM) was used as standard in this study and the synthetic molecules (3–23) have shown promising α-glucosidase inhibitory activity. Compounds 4, 8, 10, 11, 14, 18, and 21 displayed superior inhibition of α-glucosidase enzyme in the range of (IC50 = 0.53 ± 0.01–1.36 ± 0.04 μM) as compared to the standard acarbose. Compound 10 (IC50 = 0.53 ± 0.01 μM) was the most effective inhibitor of this library and displayed many folds enhanced activity in contrast to the standard. Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. This study had identified a number of potential α-glucosidase inhibitors that can be used for further research to identify a potent therapeutic agent against diabetes.

Inhibition of α-glucosidase enzyme is of prime importance for the treatment of diabetes mellitus (DM). Apart of many organic scaffolds, pyridine based compounds have previously been reported for wide range of bioactivities. The current study reports a series of pyridine based synthetic analogues for their α-glucosidase inhibitory potential assessed by in vitro, kinetics and in silico studies. For this purpose, 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitriles 1–28 were synthesized and subjected to in vitro screening. Several analogs, including 1–3, 7, 9, 11–14, and 16 showed many folds increased inhibitory potential in comparison to the standard acarbose (IC50 = 750 ± 10 µM). Interestingly, compound 7 (IC50 = 55.6 ± 0.3 µM) exhibited thirteen-folds greater inhibition strength than the standard acarbose. Kinetic studies on most potent molecule 7 revealed a competitive type inhibitory mechanism. In silico studies have been performed to examine the binding mode of ligand (compound 7) with the active site residues of α-glucosidase enzyme.

5-Arylidene-N,N-diethylthiobarbiturates 1-25 were evaluated for their potential against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and displayed varying degree of inhibition. Based on the IC50 values, compound 6 (IC50 = 92.51 and#177; 0.01 and#181;M) was the only active compound against acetylcholinesterase, however this compound was also weakly active against butyrylcholinesterase with an IC50 value 124.76 and#177; 0.02 and#181;M. Six compounds 1, 6, 7, 16, 17, and 18 showed weak inhibition against BChE, among them compound 18 (IC50 = 82.25 and#177; 0.07and#181;M) showed good inhibition against BChE. Nevertheless, compounds 1, 7, 16, 17, and 18 were selectively active against BChE enzyme.

Current research deals with the biology-oriented drug synthesis (BIODS) of twenty-three new thiourea analogs of pharmacologically important drug atenolol which is a well-known medicine to treat hypertension as well as cardiovascular diseases (CVDs). Structural characterization of all compounds was done by various spectroscopic techniques. Compounds 1–23 were subjected for urease inhibitory activity in vitro. Screening results revealed that whole library was found to be active having IC50 ranges from 11.73 ± 0.28 to 212.24 ± 0.42 µM. It is noteworthy that several derivatives including 3 (IC50 = 21.65 ± 0.31 µM), 8 (IC50 = 19.26 ± 0.42 µM), 9 (IC50 = 21.27 ± 0.25 µM), 12 (IC50 = 21.52 ± 0.42 µM), 17 (IC50 = 19.26 ± 0.42 µM), 20 (IC50 = 16.78 ± 0.34 µM), and 22 (IC50 = 11.73 ± 0.28 µM) showed excellent inhibitory potential than parent atenolol (IC50 = 64.36 ± 0.19 µM) and standard thiourea (IC50 = 21.74 ± 1.76 µM). A most probable structure–activity relationship (SAR) was anticipated by observing varying degree of inhibitory potential given by compounds. However, molecular insights regarding the binding mode of atenolol thiourea analogs within the active pocket of urease enzyme was rationalized by molecular docking studies.

Overexpression of NTPDases leads to a number of pathological situations such as thrombosis, and cancer. Thus, effective inhibitors are required to combat these pathological situations. Different classes of NTPDase inhibitors are reported so far including nucleotides and their derivatives, sulfonated dyes such as reactive blue 2, suramin and its derivatives, and polyoxomatalates (POMs). Suramin is a well-known and potent NTPDase inhibitor, nonetheless, a range of side effects are also associated with it. Reactive blue 2 also had non-specific side effects that become apparent at high concentrations. In addition, most of the NTPDase inhibitors are high molecular weight compounds, always required tedious chemical steps to synthesize. Hence, there is still need to explore novel, low molecular weight, easy to synthesize, and potent NTPDase inhibitors. Keeping in mind the known NTPDase inhibitors with imine functionality and nitrogen heterocycles, Schiff bases of tryptamine, 1–26, were synthesized and characterized by spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C NMR. All the synthetic compounds were evaluated for the inhibitory avidity against activities of three major isoforms of NTPDases: NTPDase-1, NTPDase-3, and NTPDase-8. Cumulatively, eighteen compounds were found to show potent inhibition (Ki = 0.0200–0.350 μM) of NTPDase-1, twelve (Ki = 0.071–1.060 μM) of NTPDase-3, and fifteen compounds inhibited (Ki = 0.0700–4.03 μM) NTPDase-8 activity. As a comparison, the Kis of the standard inhibitor suramin were 1.260 ± 0.007, 6.39 ± 0.89 and 1.180 ± 0.002 μM, respectively. Kinetic studies were performed on lead compounds (6, 5, and 21) with human (h-) NTPDase-1, -3, and -8, and Lineweaver-Burk plot analysis showed that they were all competitive inhibitors. In silico study was conducted on compound 6 that showed the highest level of inhibition of NTPDase-1 to understand the binding mode in the active site of the enzyme.

The current study deals with the synthesis of urea and thiourea derivatives 1-37 which were characterized by various spectroscopic techniques including FAB-MS, 1H-, and 13C NMR. The synthetic compounds were subjected to urease inhibitory activity and compounds exhibited good to moderate urease inhibitory activity having IC50 values in range of 10.11-69.80 µM. Compound 1 (IC50 = 10.11 ± 0.11 µM) was found to be most active and even better as compared to the standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). A limited structure-activity relationship (SAR) was established and the compounds were also subjected to docking studies to confirm the binding interactions of ligands (compounds) with the active site of enzyme.

Current study is based on the biology-oriented drug synthesis (BIODS) of S-naproxen (NSAID) derivatives and the evaluation of their urease inhibitory potential. In this regard, a variety of S-naproxen derivatives 2–39 including hydrazide 1, Schiff bases 2–21, aroyl substituted hydrazides 22–24, sulfohydrazides 25–34, 2-mercapto oxadiazole 35, phenacyl substituted 2-mercapto oxadiazoles 36–39 were synthesized under the umbrella of BIODS by simple chemical transformation of its pharmacophoric carboxylic group. Compounds 1–39 were evaluated for in vitro urease inhibitory activity and most of them showed good to moderate inhibitory potential in the range of IC50 = 14.01 ± 0.23–76.43 ± 0.8 µM as compared to standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Limited structure-activity relationship (SAR) was established in order to rationalize the participation of varying groups (R) in the inhibitory potential of compounds. Molecular docking study on all active compounds was also carried out to decipher the interactions detail of the ligand with the receptors of active site of enzyme.

A series of 1-[(4′-chlorophenyl)carbonyl-4-(aryl)thiosemicarbazide derivatives 1–25 was synthesized and characterized by spectroscopic techniques such as EI-MS and 1H NMR. All compounds were screened for urease inhibitory activity in vitro and demonstrated excellent inhibitory activity in the range of IC50 = 0.32 ± 0.01–25.13 ± 0.13 μM as compared to the standard thiourea (IC50 = 21.25 ± 0.13 μM). Amongst the potent analogs, compounds 3 (IC50 = 2.31 ± 0.01 μM), 6 (IC50 = 2.14 ± 0.04 μM), 10 (IC50 = 1.14 ± 0.06 μM), 20 (IC50 = 2.15 ± 0.05 μM), and 25 (IC50 = 0.32 ± 0.01 μM) are many folds more active than the standard. Structure-activity relationship (SAR) was rationalized by looking at the effect of diversely substituted aryl ring on inhibitory potential which predicted that regardless of the nature of substituents, their positions on aryl ring is worth important for the potent activity. Furthermore, to verify these interpretations, in silico study was performed on all compounds and a good correlation was perceived between the biological evaluation and docking study of compounds.

Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1–13 and bis-chalcones 14–18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50 = 1.25 ± 1.05–2.40 ± 0.09 µM as compared to the standard acarbose (IC50 = 1.04 ± 0.3 µM). Limited structure–activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.

In this study, twenty-nine 2-aminopyrimidine derivatives are synthesized in good to excellent yields by fusing 2-amino-4,6-dichloropyrimidine with different amines in the presence of triethylamine without using any solvent or catalyst. Nucleophilic substitution reactions of 2-amino-4,6-dichloropyrimidine with amines have also been performed in ethanol. Comparisons of the yields and reaction times for both solvent and solvent-free conditions have shown that the newly developed solvent-free protocol is high yielding, more efficient, and simpler compared to conventional methods.

This article pertains to development and validation of a low cost, fast, sensitive, and accurate RP-HPLC method for quantitative analysis of HZ. A Hibar μBondapak C18 column as the stationary phase and acetonitrile:methanol:buffer (500:200:300) as the mobile phase were used to accomplish the separation, when drawn at a flow rate of 1.0 mL/min, with 235 nm as monitoring wavelength. Linearity was established by studying the drug over the concentration range of 10–10000 ng mL−1, correlation coefficient of r = 0.9993, drug recovery (97 to 102%), and high reproducibility in serum samples (less than 2.5% RSD) displayed excellent linearity, accuracy, and precision. Force degradation studies of the drug under various stress conditions (acid, base, oxidation, photo, and thermal) proved the stability indicating power of the method. Substantial method validation study was carried out inline with ICH guidelines and was applied successfully to quantify the amount of HZ in bulk, pharmaceutical formulations, and blood s...

5-Aryl-1H-tetrazoles (1–24) were synthesized and screened for their xanthine oxidase (XO) inhibitory activity using allopurinol as standard inhibitor (IC50 = 2.0 ± 0.01 µM). Six compounds 3, 4, 5, 9, 21, and 24 exhibited significant to weak activities with IC50 values in the range of 7.4–174.2 µM. Active compounds were further subjected to kinetic and molecular docking studies to deduce their modes of inhibition, and to study their interactions with the protein (XO) at atomic level, respectively. Interestingly, all these compounds showed a competitive mode of inhibition. Docking studies identified several important interactions between the ligand and the receptor protein (XO). Some of these interactions were similar to that exhibited by clinical inhibitors of XO (allopurinol, and febuxostat). This study identifies 5-aryl-1H-tetrazoles as a new class of xanthine oxidase inhibitors, which deserves to be further, investigated for the treatment of hyperuricemia and gout.

5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones 1-43 were synthesized in a "one-pot" three component reaction and structurally characterized by various spectroscopic techniques such as 1H, 13C NMR, EI-MS, HREI-MS, and IR. All compounds were evaluated for their in vitro urease inhibitory activity. It is worth mentioning that except derivatives 1, 11, 12, and 14, all were found to be more potent than the standard thiourea (IC50 = 21.25 ± 0.15 µM) and showed their urease inhibitory potential in the range of IC50 = 3.70 ± 0.5-20.14 ± 0.1 µM. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules. However, molecular modeling study was performed to confirm the binding interactions of the molecules (ligand) with the active site of enzyme.

Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.

This manuscript describes the protein anti-glycation activity of thirty-three (33) benzothiazoles, out of which twenty-seven were the newly synthesized benzothiazoles. Compound 1 (IC 50 = 187 ± 2.6 µM) was found to be the most active, while compounds 2 (IC 50 = 219 ± 3.6 µM), 3 (IC 50 = 224 ± 1.9 µM), 4 (IC 50 = 223 ± 3.3 µM), 5 (IC 50 = 238 ± 2.2 µM), 7 (IC 50 = 266 ± 5.4 µM), 17 (IC 50 = 226 ± 1.6 µM) and 18 (IC 50 = 274 ± 2.4 µM) were significantly active, when compared with the standard rutin (IC 50 = 294 ± 1.5 µM). This study identified potential inhibitors of methylglyoxal mediated glycation of proteins, which is the pathophysiology of late diabetic complications.

Oxadiazoles and thiadiazoles 1-37 were synthesized and evaluated for the first time for their α-glucosidase inhibitory activities. As a result, fifteen of them 1, 4, 5, 7, 8, 13, 17, 23, 25, 30, 32, 33, 35, 36 and 37 were identified as potent inhibitors of the enzyme. Kinetic studies of the most active compounds (oxadiazoles 1, 23 and 25, and thiadiazoles 35 and 37) were carried out to determine their mode of inhibition and dissociation constants Ki. The most potent compound of the oxadiazole series (compound 23) was found to be a non-competitive inhibitor (Ki=4.36±0.017 μM), while most potent thiadiazole 35 was identified as a competitive inhibitor (Ki=6.0±0.059 μM). The selectivity and toxicity of these compounds were also studied by evaluating their potential against other enzymes, such as carbonic anhydrase-II and phosphodiesterase-I. Cytotoxicity was evaluated against rat fibroblast 3T3 cell line. Interestingly, these compounds were found to be inactive against other enzymes, exhibiting their selectivity towards α-glucosidase. Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. α-Glucosidase inhibitors can also be used as anti-obesity and anti-viral drugs. Our study identifies two novel series of potent α-glucosidase inhibitors for further investigation.

2-Arylquinazolin-4(3H)-ones 1–25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1–25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6–198.2 μM, was observed and compared with the standard d -saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6–44.0 μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure–activity relationship is established.

A simple, experimentally rapid and efficient CsF catalyzed tandem Knoevenagel–Michael reaction protocol is developed for the synthesis of a series of functionalized 9-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-3,3-dimethyl-2,3,4,9-tetrahydro-1 H -xanthen-1-one ( 1 – 7 ) by reacting dimedone with substituted salicylaldehydes. The use of CsF as a catalyst allowed reactions under moderate conditions and resulted in better yields.

Current research is based on the synthesis of novel ( E )-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives ( 3 – 15 ) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde ( 1 ) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate ( 2 ). While in second step, cyclization between the intermediate ( 2 ) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1 H NMR and 13 C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2 – 15 were subjected for in vitro β -glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC 50 = 3.10 ± 0.10–40.10 ± 0.90 μM and found to be even more potent than the standard d -saccharic acid 1,4-lactone (IC 50 = 48.38 ± 1.05 μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds.

This paper reports a rapid, simple, and sensitive method for determination of vitamin D3, vitamin E acetate, and vitamin K1 in plasma using atmospheric pressure chemical ionization –high performance liquid chromatography–mass spectrometry. Plasma samples were prepared using solid phase extraction. The separation of compounds was achieved using a C18 monolithic column and a mobile phase composed of methanol and 0.1% formic acid in gradient elution mode at a flow rate of 1.0 mL min−1. Analytes were ionized using atmospheric chemical ionization in positive mode. Mass spectra were recorded at m/z = 385.23, 473.47, and 451.41 for vitamin D3, vitamin E, and vitamin K1, respectively. Vitamin D2 was used as an internal standard and its mass spectra was recorded at 397.28 m/z. The method was validated using ICH guidelines. The system suitability responses were calculated for retention time, number of theoretical plates, capacity factor, resolution, and the selectivity factor. System validation was evaluated for pr...

Twenty-one novel urea derivatives were synthesized and their structures characterized by mass, NMR, IR, and UV spectroscopy. These compounds were evaluated for their antiproliferative profile against human PC-3 (prostate) and NCI-H460 (lung) cancer cell lines. Among them, compound 21 N-(3-nitrophenyl)-N′-(1-phenylethyl)urea was found to be active against both PC-3 (IC50 ± SEM: 20.13 ± 0.91 μM) and NCI-H460 (GI50: 22 ± 2.6 μM) cell lines; hence has the potential to be further studied as anticancer agent. These compounds were also investigated for their ability to inhibit urease, β-glucuronidase, and phosphodiesterase enzymes. N-(2,6-Dimethylphenyl)-N′-(4′-nitrophenyl)urea (1) demonstrated 90 % inhibition of β-glucuronidase enzyme (IC50 ± SEM: 3.38 ± 0.043 μM).

Thiadiazole derivatives 1–24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC50 = 2.16 ± 0.01–58.06 ± 1.60 μM as compare to standard d -saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure–activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques 1H, 13C NMR, and EIMS.

Liquid chromatography-mass spectrometry (LC-MS) in atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) modes were studied for a multi-component plasma and urine quantification of 5 antihyperglycemic agents (metformin, pioglitazone, gliclazide, glibenclamide, and glimperide). The separation of the compounds was achieved using Chromolith Performance RP-18e column (100 × 4.6 mm), with gradient mobile phase composition of acetonitrile −0.1% formic acid. MS parameters for APCI and ESI were optimized individually and were operated in positive mode. The detection limits for the metformin, pioglitazone, glibenclamide, and glimepiride were determined to be 6.84, 6.22, 13.03, and 44.38 ng mL−1 using LC-ESI-MS; and for LC-APCI-MS, it was determined to be 48.39, 8.02, 17.02, and 144.55 ng mL−1, respectively. Gliclazide was the only exception as it exhibited a lower limit of detection (LOD) using APCI than ESI which was found to be 5.61 and 23.43 ng mL−1, respectively. The method was vali...

Benzothiazole derivatives 1 – 26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC 50 = 8.9 ± 0.25 μM), 5 (IC 50 = 36.1 ± 1.80 μM), 8 (IC 50 = 8.9 ± 0.38 μM), 13 (IC 50 = 19.4 ± 1.00 μM), 16 (IC 50 = 4.23 ± 0.054 μM), and 18 (IC 50 = 2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard ( d -saccharic acid 1,4-lactone, IC 50 = 48.4 ± 1.25 μM). Compound 9 (IC 50 = 94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors.

An eco-benign method for the synthesis of title compounds (III) is developed using NH4Cl in stoichiometric amount as enolization activator in water.

The reaction of isocyanates and isothiocyanates with long-chain alcohols, e.g. n-hexanol, n-heptanol and n-octanol, exclusively gave N-aryl-O-alkyl carbamates, while N-aryl-O-alkyl carbamates were formed along with symmetrical 1,3-disubstituted ureas and thioureas when the same reactions were carried out with small-chain alcohols at room temperature without using any solvent.