Thiazolopyridine analogs of naldixic acid. 1. Thiazolo[5,4-b]pyridines

A series of 2-substituted-7-alkyl-4,7-dihydro-4-oxothiazolo[5,4-b]pyridine-5-carboxylic acids were synthesized. Antibacterial activity was tested in vitro. None of the new compounds prepared showed any antibacterial activity in vitro against the strains tested.     

In vitro avarol does affect the growth of Candida sp.

This work extends in vitro screening of antimicrobial activity of avarol, the marine natural product firstly isolated from the Mediterranean sponge Dysidea avara. Its anticandidial activity was evaluated by microdilution method against eight Candida strains, two ATCC and six clinical ones. At a different extent this compound was proven to be active against all the strains tested (MIC 0.8–6.0 μg/mL and MFC 1.6–12.0 μg/mL, respectively). According to the best of our knowledge, this is the first report on avarol activity towards any yeast strain which may be of relevance for Alzheimer’s disease. Indeed, avarol derivatives showing moderate AChE activity should be screened for anticandidial activity both in vitro and in vivo.     

Streptonigrin and related compounds. 6. Synthesis and activity of some quinoxaline analogues

Streptonigrin is an antitumor antibiotic with significant in vitro and in vivo antitumor activity spectrum. Besides the total syntheses, numerous syntheses of the partial structures have been carried out in order to assess the structural requirements for the activity. The present publication deals with the synthesis of selected quinoxalinequinones to study the effect of changes in the B-ring of streptonigrin. A convenient 3-step synthesis of the required quinoxaline starting material that provides the necessary control of the desired substituent pattern is described. A series of 7-amino-6-methoxy-quinoxalinequinones were prepared in which substitution at 3- was varied (from H to Cl, OCH₃, CN, COOCH₃ and OH). A few selected 6-aminoquinones (with 6-NH₂ and 6-piperidinyl) were also prepared for comparison. The quinones (18) were tested in three different in vitro test systems: cytotoxicity to mouse leukemia (L-1210) cells, antibacterial activity against Bacillus subtilis and inhibition of root growth. Several of the aminoquinones showed significant activity in comparison to that shown by streptonigrin.     

A new triterpenoid from the fruits of Gardenia jasminoides var. radicans Makino

A novel triterpenoid 3α,16β,23,24-tetrahydroxy-28-nor-ursane-12,17,19,21-tetraen (1) was isolated from the fruits of Gardenia jasminoides var. radicans Makino. The structure of the new compounds was elucidated on the basis of spectroscopic analysis including MS and NMR data. Compound 1 was in vitro tested for cytostatic activity on human throat cancer (Hep-2) cell line by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide method and showed mild anticancer activity with the IC₅₀ of 31.2 μM.     

Three New Triterpenes from Xylarialean sp. A45, an Endophytic Fungus from Annona squamosa L.

From the fermentation extract of Xylarialean sp. A45, an endophytic fungus of Annona squamosa L., three new triterpenes, namely xylariacins A–C ( 1 – 3 , resp.) were obtained. Their structures were determined by spectroscopic analyses, including 1D‐ and 2D‐NMR experiments and HR‐ESI‐Q‐TOF mass spectrometry. The in vitro cytotoxic activities of compounds 1 – 3 were tested against human tumor cell line HepG2, and these compounds showed modest cytotoxic activity.     

Anti-inflammatory and antiproliferative activities of Ixora brevifolia Benth. (Rubiaceae)

The crude extract and fractions from the branches of Ixora brevifolia, a tree found in the Brazilian Cerrado, were tested for anti-inflammatory and in vitro antiproliferative effects. The crude extract and n-hexane fraction exhibited significant inhibition of ear oedema in mice, while n-hexane-precipitated and chloroform fractions strongly inhibited the myeloperoxidase activity in ear tissue. The n-hexane and n-hexane-precipitated fractions showed strong growth inhibition for glioma cell line and the hydromethanolic fraction inhibited the growth of leukaemia cell line.     

Folate antagonists. 14. Synthesis of pyrazino[2,3-f]quinazoline-8,10-diamines and related heterocycles as potential antimalarial agents (1,2)

Amination of 5-chloro-6-nitro-2,4-quinazolinediamine ( 2 ) afforded 6-nitro-2,4,5-quinazolinetriamine ( 3 ) which was hydrogenated catalytically to produce 2,4,5,6-quinazolinetetraamine ( 5 ). Condensation of 5 with the requisite diketones afforded 8,9,10,11-tetrahydropyrimido[5,4-a]-phenazine-1,3-diamine ( 6 ), several pyrazino[2,3-f]quinazoline-8,10-diamines ( 7–10,13 ) as well as two pyrimido[4,5-f]phenazinediamines ( 11,12 ). Amination of 2 in the presence of formamide at 120° led to the formation of 9-nitro-1H-pyrimido[4,5,6-de]quinazolin-5-amine ( 4 ). None of these compounds showed suppressive activity when tested parenterally against lethal Plasmodium berghei infections in mice. When tested against various bacteria in vitro, 7 and 10 exhibited activity against Streptococcus faecalis at a concentration below 2.5 μg./ml.     

Antibacterial and antifungal ferrocene incorporated dithiothione and dithioketone compounds

Two antibacterial and antifungal ferrocene incorporated compounds have been synthesized, characterized and screened for their in vitro antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysenteriae, Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureus and Streptococcus pyogenes bacterial strains and for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. Results show that these compounds have significant activity against tested bacterial and fungal strains and thus introduce a novel class of ferrocene incorporating antibacterial and antifungal compounds. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis,characterization and in vitro antiprotozoal studies of iron(III) complexes of some antimalarial drugs

We present the synthesis, characterization and in vitro antiplasmodial and antitrypanosomal studies of iron(III) complexes of amodiaquine, trimethoprim and pyrimethamine. The complexes have been characterized by elemental analyses, electronic and IR spectroscopy and room temperature magnetic susceptibility measurements. The spectra are consistent with octahedral geometry around the metal ions. The complexes were tested for in vitro activity against cultures of Plasmodium falciparum, Tripanosoma brucei rhodosiense, L. donovani and Tripanosoma cruzi. One of the complexes showed enhanced activity of about 8.4 times more than chloroquine against the resistant strain of Plasmodium falciparum.     

A new tetracyclic saponin from Astragalus glycyphyllos L. and its neuroprotective and hMAO-B inhibiting activity

Abstract

A new tetracyclic saponin, 17(R),20(R)-3β,6α,16β-trihydroxycycloartanyl-23-carboxylic acid 16-lactone 3-O-β-D-glucopyranoside (1) together with one known flavonoid, camelliaside A (2) were isolated from the aerial parts of Astragalus glycyphyllos L. Their structures were determined by chemical, HRESIMS and NMR methods. On 6-hydroxydopamine in vitro model on isolated rat brain synaptosomes, compounds 1–2 had statistically significant neuroprotective activity similar to that of Silibinin, tested at 100?μM. Saponin 1 possessed the most prominent neuroprotective and antioxidant effects in this in vitro model. On human recombinant monoamine oxidase type B enzyme compound 1 displayed strong inhibiting activity, compared to Selegiline (1?μM). It could be concluded that the new epoxycycloartane saponin 1 could be a promising leading structure in respect of neurodegenerative diseases.     

Studies on Antifungal Agents. Part 25. 1-[(3,5-Bisaryl-2-methylisoxazolidin-3-yl)methyl]-1H-1,2,4-triazoles

The synthesis and antifungal activity of a novel series of 1-[(3,5-bisaryl-2-methylisoxazolidin-3-yl)methyl]-1H-1,2,4-triazoles 6 and 7 (i.e. 8 – 19 ) are discussed. The preparation of 8 – 19 was straightforward and highlighted by a regiospecific 1,3-dipolar cycloaddition of α-substituted (E)-ketonitrones 4 with appropriate atyrene derivatives 5 that led to a cis/trans-diastereoisomeric mixture of the corresponding triazoles (Scheme). The title compounds were evaluated for in vitro antifungal activity in solid agar cultures against a broad array of yeast and systemic mycoses and dermatophytes. The in vivo activity was determined in an immune-compromised mouse model of systemic candidiasis. While the in vitro activity was evident throughout the series, it was moderate in potency. However, some of the triazole derivatives demonstrated a potent in vivo activity comparable to that of the standard drug ketoconazole. Analogue 12 (PR 988-399) emerged as the best overall compound demonstrating potent antifungal activity in both in vitro and in vivo assays.     

Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives

A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro.It was found that most of the tested compounds especially compound 17, shown stronger activity to the selected three cell lines than ZM447439.     

Chemical composition and antibacterial activity of essential oil of Nepeta graciliflora Benth. (Lamiaceae)

The chemical composition of the essential oil obtained from aerial parts of Nepeta graciliflora was analysed, for the first time, by GC–FID and GC–MS. A total of 27 compounds were identified, constituting over 91.44% of oil composition. The oil was strongly characterised by sesquiterpenes (86.72%), with β-sesquiphellandrene (28.75%), caryophyllene oxide (12.15%), α-bisabolol (8.97%), α-bergamotene (8.51%), β-bisabolene (6.33%) and β-Caryophyllene (5.34%) as the main constituents. The in vitro activity of the essential oil was determined against four micro-organisms in comparison with chloramphenicol by the agar well diffusion and broth dilution method. The oil exhibited good activity against all tested organisms.     

Synthesis of 1,4-Benzothiazine Compounds Containing Isatin Hydrazone Moiety as Antimicrobial Agent

A series of novel 3‐methyl‐N"‐(2‐oxoindolin‐3‐ylidene)‐4H‐benzo[b][1,4]thiazine‐2‐carbohyrazides have been synthesized and studied on their in vitro antimicrobial activity potency to establish structure‐activity relationship. Several compounds demonstrated promising antifungal and antibacterial activity; however, other tested compounds exhibited moderate to poor antimicrobial activity with respect to the reference drug against the test strains.     

1H‐1,2,3‐Triazole‐tethered Isatin–coumarin Hybrids: Design,Synthesis and In Vitro Anti‐mycobacterial Evaluation

A series of novel 1H‐1,2,3‐triazole‐tethered isatin–coumarin hybrids 7a – l integrate three anti‐tuberculosis bioactive substances/pharmacophoric units including coumarin, isatin, and I ‐ A09 were designed, synthesized, and tested for their in vitro anti‐mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv as well as cytotoxicity in VERO cell line. The results showed that all hybrids exhibited weak to moderate activity against the tested two strains with minimum inhibitory concentration ranging from 50 to 200 μg/mL.     

Novel silicon-containing drugs derived from the indomethacin scaffold: Synthesis, characterization and evaluation of biological activity

Synthesis, spectroscopic characterization and in vitro pharmacological and cancer cell growth inhibitory activity studies of new silicon-containing compounds based on the indomethacin scaffold are now reported. Amidation of the indomethacin carboxylate group using amino-functional silanes generated a series of novel lipophilic derivatives of indomethacin. The pharmacological activity of these derivatives tested against human recombinant cyclooxygenase-1 and 2 demonstrated that the silicon-containing derivatives are cyclooxygenase-2 (COX-2) selective. The silicon-containing amides of indomethacin demonstrated in vitro growth inhibitory activity against human MiaPaCa-2 pancreatic carcinoma cells at low μM concentrations. The 3a and 3c derivatives exhibited the most potent in vitro antiproliferative activity, with IC₅₀ <6.0 μM, compared to unmodified indomethacin having an IC₅₀100 μM. We dedicate this paper to Prof. Mitsuo Kira, outstanding organosilicon chemist and valued friend.     

Synthesis and antimicrobial evaluation of 6-azauracil non-nucleosides

The present study describes synthesis and antimicrobial evaluation of a series of novel 6-azauracil non-nucleosides. Reaction of silylated 6-azauracils with the appropriate chloroethers gave the corresponding non-nucleosides. 1-(Allyloxymethy)-6-azauracils and non-nucleosides bearing indanyl, cyclohexenyl, and cyclohexyl moieties were obtained via silylation of 6-azauracils followed by treatment with the appropriate acetals. Selected compounds were tested for their in vitro antimicrobial activity against a panel of standard strains of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Four compounds showed marked inhibitory activity particularly against the tested Gram-positive bacteria.     

Synthesis and biological activity of 1-, 2- or 3-Substituted benzothieno-[2,3-d]triazole derivatives structurally related to trazodone

A series of new 1-, 2- and 3-piperazinylbenzothieno[2,3-d]triazole derivatives structurally related to Trazodone were prepared and tested for their antiserotonergic, antiadrenergic and antihistaminergic in vitro activities together with their analgesic in vivo activity by using Trazodone as the reference compound.     

Synthesis of benzimidazo-substituted 3-quinolinecarboxylic acids as antibacterial agents

The 6- and 7-(1-ethylbenzimidazolyl)-substituted 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids were synthesized. Antibacterial activity was tested in vitro. Only one of the new compounds prepared showed slight antibacterial activity against one of the strains tested. So, they are of no interest as antibacterial agents.     

Synthesis and xanthine oxidase inhibitory activity of 4,6-disubstituted 1-p-chlorophenylpyrazolo[3,4-d]pyrimidines

Several 4,6-disubstituted 1-p-chlorophenylpyrazolo[3,4-d]pyrimidines were prepared from 4,6-dichloro-1-p-chlorophenylpyrazolo[3,4-d]pyrimidine and their xanthine oxidase inhibitory activity were tested in vitro.