In vitro and in silico studies of fluorinated 2,3-disubstituted thiazolidinone-pyrazoles as potential α-amylase inhibitors and antioxidant agents.

As part of our effort to identify potent α-amylase inhibitors, in the present study, a novel series of fluorinated thiazolidinone-pyrazole hybrid molecules were prepared by the condensation of 3-(aryl/benzyloxyaryl)-pyrazole-4-carbaldehydes with fluorinated 2,3-disubstituted thiazolidin-4-ones. The structures of the newly synthesized compounds were confirmed by infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and liquid chromatography-mass spectrometry data. All the compounds were screened for their α-amylase inhibitory and free radical scavenging activities by DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS methods. Among the tested compounds, compound 8g emerged as a promising α-amylase inhibitor with IC50 = 0.76 ± 1.23 µM, and it was found to be more potent than the standard drug acarbose (IC50 = 0.86 ± 0.81 µM). Compounds 8b and 8g showed strong free radical scavenging activity compared to the standard butylated hydroxyl anisole. The kinetic study of compound 8g revealed the reversible, classical competitive inhibition mode on the α-amylase enzyme. Molecular docking and dynamic simulations studies were performed for the most potent compound 8g, which displayed remarkable hydrogen bonding with the α-amylase protein (PDB ID: 1DHK).

Adverse childhood experiences and substance misuse in young people in India: results from the multisite cVEDA cohort.

BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).

High performance thin layer chromatography qualitative densitometry as a sensitive method to assess shelf life of polyherbal formulations: A study on Hutabhugadi Churna.

INTRODUCTION: Measuring chemical stability of polyherbal formulations is very challenging due to diversity in phytochemical composition. As there are no comprehensive guidelines for stability testing of herbal products, there is a need for a sensitive tool to detect how the quality of herbal products varies with time under the influence of environmental conditions. AIMS: To validate the employability of high-performance thin layer chromatography (HPTLC) for real-time stability of Hutabhugadi Churna (HC). MATERIALS AND METHODS: The chromatograms were developed using toluene/ethyl acetate/formic acid (10:5:1) and ethyl acetate/formic acid (10:1) as a mobile phase for chloroform and ethanolic extract, respectively. The plates were scanned under 254, 366, 540 (pre-derivatization) and 540 nm (post-derivatization). Samples were analyzed immediately after preparation and after 3(rd) and 6(th) months of storage. Alteration of fingerprint profiles from the initial pattern, in terms of number of peaks, was employed as diagnostic tools. Percentage variation in composition at given period was calculated. RESULTS: HC is found to be stable at room temperature up to 1.3 months using the method of calculation of 10% degradation period employing slope and intercept values for the initial, 3(rd) and 6(th) months' deviation in number of bands. The data obtained were subjected to regression analysis in context to number of bands obtained. The curve was found to be linear with R(2) value of 0.89-0.96 supported by their tolerance range of 0.04-0.11. CONCLUSION: The proposed model is a new logic with prospects to become working method for stability assessment of polyherbal formulations under controlled conditions.

Synthesis and antitumor activity studies of some new fused 1,2,4-triazole derivatives carrying 2,4-dichloro-5-fluorophenyl moiety.

A series of 3-(2,4-dichloro-5-fluorophenyl)-6-(substituted phenyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (4) (Fig. 1) have been synthesized by the cyclization of 3-(2,4-dichloro-5-fluorophenyl)-1,2,4-triazol-5-thiol (3) with substituted phenacyl bromides. All the newly synthesized compounds were confirmed by IR, (1)H NMR and mass spectral studies. Among the compounds tested for their antitumor activity three compounds exhibited in vitro antitumor activity with moderate to excellent growth inhibition against a panel of sixty cancer cell lines of leukemia, non-small cell lung cancer, melanoma, ovarian cancer, prostate and breast cancer. The compound 4d showed promising antiproliferative activity with GI(50) values in the range of 1.06-25.4 microM.

Synthesis and antimicrobial activities of some new triazolothiadiazoles bearing 4-methylthiobenzyl moiety.

A series of substituted triazolothiadiazoles have been synthesized by condensing 4-amino-3-[4-methylthiobenzyl]-4H-1,2,4-triazole-5-thiol (5) with substituted aryl furoic acids/aromatic acids in the presence of POCl3. The triazole (5) was obtained by the fusion of 4-methylthiophenyl acetic acid with thiocarbohydrazide. The structures of newly synthesized compounds are characterized by elemental analysis, IR, 1H NMR and mass spectroscopic studies and were screened for their antimicrobial activities. The preliminary results revealed that some of the compounds exhibited promising antimicrobial activities.

(2E)-1-(4-Methyl-phen-yl)-3-(2,3,5-trichloro-phen-yl)prop-2-en-1-one.

In the title mol-ecule, C(16)H(11)Cl(3)O, the dihedral angle between the two benzene rings is 33.2 (1)°. The crystal packing is stabilized by C-H⋯O hydrogen bonds.

2-(2-Methoxy-phen-yl)-4,4-dimethyl-4,5-dihydro-1,3-oxazole.

In the title mol-ecule, C(12)H(15)NO(2), the oxazole ring adopts an envelope conformation. Overall, the mol-ecule is approximately planar, the dihedral angle between the mean plane through all but the methyl-ene C atom of the five-membered ring and the aromatic ring being 8.6 (1)°. A weak C-H⋯O inter-action contributes to the stabilization of the crystal structure.

Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents.

Synthesis of a series of 7-arylidene-6-(2,4-dichlorophenyl)-3-aryloxymethyl/anilinomethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) by the condensation of 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-propen-1-one (1) and 4-amino-5-mercapto-3-aryloxymethyl/anilinomethyl-1,2,4-triazoles (2) is described. The newly synthesized compounds were characterized by elemental analysis IR, 1H NMR and mass spectral data. These compounds were tested for their antimicrobial activities against Escherichia coli, Staphylococcus aureus (Smith), Psuedomonas aeruginosa (Gessard), Bacillus subtilis and Candida albicans. Some of the newly synthesized compounds were also screened for their anticancer activity. Among them compounds 3m, 3o, 3q showed in vitro anticancer activity.

One pot synthesis of thiazolodihydropyrimidinones and evaluation of their anticancer activity.

2-(5-Arylfurfurylidene/5-nitrofurfurylidene)-5-aryl-7-(2,4-dichloro-5-fluorophenyl)-5H-thiazolo[2,3-b]-pyrimidin-2(1H)-ones 5 and 6 are synthesized by a novel three component reaction of 4,6-diarylpyrimidino-2(1H)-thiones 4, monochloroacetic acid, arylfurfuraldehydes and 5-nitro-2-furfuraldenediacetate, respectively. The newly synthesized compounds are characterized by elemental analysis, IR, (1)H NMR and mass spectral studies. These compounds exhibited in vitro antitumour activity with moderate to excellent growth inhibition against a panel of 60 cell lines of leukemia, non-small cell lung cancer melanoma, ovarian cancer, prostate cancer and breast cancer.

Synthesis characterization and anticancer activity studies on some Mannich bases derived from 1,2,4-triazoles.

A series of 3-substituted 4-[5-(4-methoxy-2-nitrophenyl)-2-furfurylidene] amino-5-mercapto-1,2,4-triazoles (3) were synthesized. Aminomethylation of compounds 3 with formaldehyde and various secondary amines furnished Mannich bases 4 and 5. These compounds were characterized on the basis of IR, 1H-NMR, mass spectral data and elemental analysis. The newly synthesized compounds were screened for their anticancer activity against a panel of 60 cell lines derived from seven cancer types namely, lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the compounds were slightly more potent.

Synthetic and antibacterial studies on some new furanopeptides.

A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent. Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis. Some of the selected compounds are also tested for their antibacterial properties.

Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents.

A series of arylthioureas (1), aromatic aldehyde thiosemicarbazones (2) and 5-aryl-2-furfuraldehyde thiosemicarbazones (3) were condensed with 2,4-dichloro-5-fluorophenacyl bromide to yield respective arylaminothiazoles, arylidene/5-aryl-2-furfurylidene hydrazinothiazoles (4). The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral studies. These compounds were also screened for their antibacterial and anti-inflammatory activities. Two of the newly synthesized compounds showed anti-inflammatory activity comparable with that of Ibuprofen.

Synthesis of some new biologically active thiadiazolotriazinones--part III.

4-Amino-6-arylmethyl/tert-butyl-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with arylfuroic acids (2) to yield 7-(5-aryl-2-furyl)-3-arylmethyl/tert-butyl-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-4-ones (3). The newly synthesized compounds exhibited antibacterial activity comparable to that of nitrofurazone. In addition, two compounds displayed in vitro antitumor activity with moderate growth inhibition against a panel of 60 tumor cell lines.

New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents.

A series of bis-phenoxyacetic acids 2 were prepared starting from corresponding unsubstituted/substituted 1,4-quinols 1. The fusion of bis-phenoxyacetic acids 2 with thiocarbohydrazide gave the corresponding bis-[4-amino-5-mercapto-1,2,4-triazol-3-yl-methyleneoxy]phenylenes (3) in a one pot reaction. The reaction of bis-triazoles 3 with various reagents afforded N-bridged heterocycles 4-6 in good yields. The newly synthesised compounds were screened for their anticancer activity against a panel of 60 cell lines derived from seven cancer types namely, lung, colon, melanoma, renal, ovarian, CNS and leukemia. Some of the tested compounds showed promising anticancer properties.

Synthesis, characterization and antibacterial activities of some N-bridged heterocycles containing triazole, quinoline and nitrofuran moieties.

A series of 2-(2-furyl)4-quinolinecarboxylic acids (3), 2-(5-nitro-2-furyl)4-quinolinecarboxylic acids (6), 4-(3-aryloxymethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazolo-6-yl)-2-(furyl)quinolines (5) and 4-(3-aryloxymethyl-1.2,4-triazolo[3,4-b]-1,3,4-thiadiazolo-6-yl)-2-(5-nitro-2-furyl)quinolines (7) were synthesized. The structures of the newly synthesized compounds are confirmed on the basis of elemental analysis, IR, 1H-NMR and mass spectral data. The newly synthesized compounds are evaluated for their antibacterial activities. Compounds containing nitrofuran moiety showed excellent antibacterial activity. Results of such studies are disscussed in this paper.

Synthesis of some halogen-containing 1,2,4-triazolo-1,3,4-thiadiazines and their antibacterial and anticancer screening studies--part I.

A series of 7-arylidene-6-(2,4-dichloro-5-fluorophenyl)-3-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) were prepared by the condensation of 4-amino-5-mercapto-3-substituted-1,2,4-triazoles (1) and 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-2-propen-1-one (2). An alternative route for the synthesis of the title compound 3 has been described. The newly synthesised compounds were characterised on the basis of N-analyses, IR, 1H NMR and mass spectral data. Some of the newly synthesised compounds were tested for their antibacterial activities against Gram + ve and Gram - ve bacteria. Among the tested compounds 3n showed the highest degree of antibacterial activity against S. aureus and evaluation of the LD50 value of this compound was carried out. Some of the newly synthesised compounds were also screened for their anticancer activities. Among these, compounds 3b, 3g, 3n and 3p are found to be active against NCI-H460 (lung), MCF7 (breast), SF 268 (CNS) in the preliminary anticancer screening studies. Further, 60-cell-line anticancer studies of these compounds were carried out. The results of such studies are discussed in this paper.

Synthesis of some new biologically active bis-(thiadiazolotriazines) and bis-(thiadiazolotriazinyl) alkanes.

4-Amino-3-mercapto-1,2,4-triazin-5(4H)-ones (1) were condensed with dicarboxylic acids 2 to yield bis-(4-oxo-4H-1,3,4-thiadiazolo[2,3-c]-1,2,4-triazin-7-yl)alkanes (3b-d,f-h,j-l,n-p) and bis-thiadiazolotriazines (3a,e,i,m). All the newly synthesised compounds were characterised by analytical, IR, NMR and mass spectral studies. Some of the newly synthesised compounds were screened for their antibacterial and antifungal properties. Among the tested compounds, compound 7,7'-(1,4-butanediyl)-his-(3-t-butyl-4-oxo-4H-1,3,4-thia-diazolo[2,3-c]-1,2,4-triazine (3p) exhibited highest degree of antifungal activity.

Studies on nitrophenylfuran derivatives part Xii. synthesis, characterization, antibacterial and antiviral activities of some nitrophenylfurfurylidene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines.

Synthesis of four 1-aryl-3-[5-(p-nitrophenyl)-2-furyl]-2-propen-1-ones starting from substituted acetophenones and p-nitrophenylfurfuraldehyde is described. These propenones were then converted into corresponding dibromo derivatives which on dehydrobromination afforded alpha-bromopropenones rather than acetylenic ketones. Condensation of these dibromopropanones with 4-amino-5-mercapto-1,2,4-triazoles yielded a new class of nitrophenylfurfurylidene-1,2,4-triazolothiadiazines. The structures of nitrophenylfurfurylidene-1,2,4-triazolothiadiazines were established on the basis of analytical, IR, NMR and mass spectral studies. The formation of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines rather than 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines in the above condensation was unambiguously confirmed by X-ray crystallographic analysis of one of them. A possible mechanism is proposed to account for the formation of nitrophenylfurfurylidene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines. Some of the newly synthesized triazolothiadiazines were screened for their antibacterial and antiviral properties.

Studies on arylfuran derivatives. Part XI. Synthesis, characterisation and biological studies on some Mannich bases carrying 2,4-dichlorophenylfurfural moiety.

A series of 3-substituted-4-[5-(2,4-dichlorophenyl)-2-furfurylidine]amino-5-me rcapto-1, 2,4-triazoles (3) are synthesised. Aminomethylation of 3 with formaldehyde and a primary/secondary amine furnished Mannich bases 4 and 5. Both Schiff bases 3 and Mannich bases 4 and 5 are characterised on the basis of IR, 1H NMR, mass spectral data and elemental analysis. All the newly synthesised compounds are tested for their antibacterial activities. Some of the selected compounds are also tested for their fungicidal and herbicidal properties.

Studies on arylfuran derivatives: part X. Synthesis and antibacterial properties of arylfuryl-delta2-pyrazolines.

Arylfurylpropenones 3 were synthesized by Claisen-Schmidt condensation of arylfurfurals 1 with various substituted acetophenones 2. Cyclocondensation of these arylfurylpropenones 3 with hydrazine hydrate and phenylhydrazine furnished 1H-pyrazolines 4 and N-phenylpyrazolines 6, respectively. In order to study the structure-activity relationships, pyrazolines 4 were converted into their N-acetyl derivatives 5. The antibacterial properties of the new pyrazoline derivatives were studied.