New 5-(nitroheteroaryl)-1,3,4-thiadiazols containing acyclic amines at C-2: synthesis and SAR study for their antileishmanial activity

A novel series of 5-(5-nitrofuran-2-yl)-and 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole-2-amines bearing acyclic amine at C-2 position of thiadiazole ring were synthesized and evaluated in vitro against promastigote and amastigote forms of Leishmania major. The structure-activity of series was investigated by studying 40 compounds. The most active derivatives were hydroxypropylamino- and methoxypropylamino- analogs of 5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazole (compounds 29 and 32, respectively) with highest selectivity index (SI >12).     

Synthesis and in vitro antitumor and antimicrobial activity of some 2,3-diaryl-7-methyl-4,5,6,7-tetrahydroindazole and 3,3a,4,5,6,7-hexahydroindazole derivatives

The synthesis of a series of 2,3-diaryl-7-methyl-4,5,6,7-tetrahydroindazole and 3,3a,4,5,6,7-hexahydroindazole derivatives substituted with various biologically-active function groups with anticipated chemotherapeutic activity is described. 4-(7-methyl-3-aryl-3,3a,4,5,6,7-hexahydro-indazol-2-yl)benzenesulfonamides 2a–c, which were employed as key intermediates in this study, were synthesized by cyclocondensation of 6-arylidene-2-methylcyclohexanones 1a–c with 4-hydrazinobenzenesulfonamide hydrochloride. A detailed discussion of the reactions utilized in the preparation of the intermediate and target compounds is reported, and the structures of the newly synthesized compounds were substantiated with IR, ¹H and ¹³C NMR spectral data and elementary microanalyses. Twenty of the newly synthesized compounds were selected by National Cancer Institute (NCI), Maryland, USA, to be evaluated for their antitumor activity and the results revealed that six compounds 3c, 4d,e, 5a,d and 8c exhibited broad spectrum of antitumor activity against most of the tested tumor cell lines. In addition, the in vitro antibacterial and antifungal activities of a number of the target compounds were also tested using the Agar-diffusion method. Some of these compounds have shown significant antibacterial and mild to moderate antifungal activities.     

Synthesis and biological evaluation of some thiazole derivatives as new cholinesterase inhibitors

In the present study, some thiazole derivatives were synthesized via the ring closure reaction of 1-[2-(2-oxobenzo[d]thiazol-3(2H)-yl)acetyl]thiosemicarbazide with various phenacyl bromides. The chemical structures of the compounds were elucidated by ¹H NMR, ¹³C NMR and mass spectral data and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman’s spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. The most potent AChE inhibitor was found as compound 4e (IC₅₀?=?25.5?±?2.12 µg/mL) followed by compounds 4i (IC₅₀?=?38.50?±?2.12 µg/mL), 4c (IC₅₀?=?58.42?±?3.14 µg/mL) and 4g (IC₅₀?=?68?±?2.12 µg/mL) when compared with eserine (IC₅₀?=?0.025?±?0.01 µg/mL). Effective compounds on AChE exhibited weak inhibition on BuChE (IC₅₀ > 80 µg/mL). MTT assay indicated that the cytotoxic dose (IC₅₀?=?71.67?±?7.63 µg/mL) of compound 4e was higher than its effective dose.     

Unexpected formation of 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones: Synthesis,antibacterial and antifungal activities

New 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones 18–22 were synthesized, characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional NMR (¹H & ¹³C) spectroscopic data and evaluated for their in vitro antibacterial and antifungal activities. All the newly synthesized compounds exerted a wide range of antibacterial activities against the entire tested gram-positive and gram-negative bacterial strains except Escherichia coli. Compounds 21 and 22 exerted strong antifungal activities against Aspergillus flavus, mucor and Microsporum gypsuem. In addition, compound 20 was more potent against Rhizopus.

     

Design,synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives

Abstract

A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in?vitro against three protozoan parasites (Plasmodium falciparum, Leishmania donovani, and Trypanosoma brucei brucei). Biological results showed antiprotozoal activity with IC₅₀ values in the µM range. In addition, the in?vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.     

A STUDY OF ABANDONED ASH PONDS RECLAIMED THROUGH GREEN COVER DEVELOPMENT

Green capping is one of the popular methods to re-vegetate abandoned ash ponds of coal based thermal power plants thereby lowering the risk of contamination to the surrounding environment. It has innumerable advantages such as prevention of dust emission, checking soil erosion, stabilizing the surface areas of ash, preventing potential ground water contamination, and finally, adding native vegetation cover, which is very vital in the long term. During the early nineties and later, various reclamation projects were carried out on fly ash dumps, but until date, there have not been any initiatives to assess the alterations in physicochemical and biological properties of fly ash resulting from implementation of these reclamation projects. In the present study, three abandoned ash ponds, located in India, that were reclaimed during 1998–2003 are investigated. Marked alterations in nutritional status, microbial population, and microbial activities have been observed in reclaimed ash ponds.     

Design,synthesis, in vitro anticancer,antioxidant and antibacterial activity; DNA/BSA binding,photoleavage and docking studies of Cu(II) ternary metal complexes

Abstract

Three mononuclear, mixed ligand ternary Cu(II) complexes of 3-((Z)-1-(2-hydroxyphenylimino)ethyl)-4-hydroxy-6-methyl-2H-pyran-2-one (HEHMP) viz; [Cu-(Phen) (HEHMP)] (1a), [Cu-(Bpy)(HEHMP)] (1?b) and [Cu-Bpy(NCS)(HEHMP)] (1c) were synthesized and characterized by data obtained from various spectral techniques. The binding affinities of these complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) protein were explored by absorption and fluorescence quenching titrations. The results indicated strong affinity of the title compounds to bind with both CT-DNA and BSA. The antioxidant properties of the synthesized compounds evaluated by free-radical scavenging method using spectrophotometric technique indicated their affirmative potential activity. Gel electrophoresis experiments revealed the efficacy of metal complexes in resulting the cleavage of pBR322 supercoiled DNA. In vitro cytotoxicity studies of these complexes evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against HeLa and MCF-7 cancer cell lines indicated relatively high effectiveness of the complex 1c. Confocal microscopy signified the potential of the complexes to induce apoptosis in HeLa cell lines. In addition, the antibacterial activity of the compounds carried out by disc diffusion method revealed significantly enhanced antibacterial activity in Cu (II) ternary complexes compared to the activity of ligands in unbound form signifying the implicit role of metal ion in inducing lipophilic character.     

Synthesis,Antitumor, and DNA Binding Behavior of Novel 4-(2-Hydroxyquinolin-3-yl)-6-Phenyl-5, 6 Dihydropyrimidin Derivatives in Aqueous Medium

This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a–f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a–f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, ¹HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evulated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K_b) observed 4.3 × 10⁵ M^?1 for (2a), and 3.8 × 10⁵ M^?1 for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).     

Synthesis and Biological Evaluation of Novel 1′‐Branched and Spironucleoside Analogues

Novel anomeric spironucleosides and 1′‐cyano‐2′,3′‐didehydro‐2′,3′‐dideoxyuridine, a structural analogue of known anti‐HIV agents, were prepared by nucleophilic addition of organolithium reagents to 1′‐cyano‐2′‐deoxy‐ and 1′‐cyano‐2′‐deoxy‐2′β‐bromo‐uridine derivatives, respectively. The yield and distribution of products depended on the reaction conditions, which were studied in detail. Although none of the compounds exhibited antiviral activity, two compounds displayed cytostatic activity against both murine leukemia and human T‐lymphocyte cells.     

Synthesis and Antitumor Activity of a Heterodinucleotide of BVDU and Gemcitabine

A heterodinucleotide comprising BVDU and Gemcitabine bound together by a 5′,5′-pyrophospate bridge (BVDUp₂dFdC) has been synthesized and evaluated as antitumor agent against AH13 rat sarcoma cells. BVDUp₂dFdC showed a cytotoxicity similar to that of Gemcitabine.