Synthesis and in vitro antibacterial evaluation of N-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl] piperazinyl quinolones

A series of N-[5-(5-nitro-2-thienyl)-1,3,4-thiadiazole-2-yl]piperazinyl quinolones (7a-c) were synthesized and evaluated for in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria. The antibacterial data revealed that compounds 7a-c had strong and better activity against tested Gram-positive organisms than the reference quinolones such as ciprofloxacin, norfloxacin and enoxacin. However, all three compounds were nearly inactive against Gram-negative bacteria. Compound 7a (ciprofloxacin analogue) was the most active compound against Gram-positive bacteria (MIC=0.008-0.015 mug mL(-1)).     

Synthesis and antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles

2-Acetylbenzofuran 1 on treatment with substituted aldehydes affords the corresponding chalcones 2a-c. Treatment of the chalcones with nitromethane under Michael addition condition furnished the corresponding Michael adducts 3a-c. Cyclocondensation of the chalcones 2a and 2b with thiosemicarbazide under basic refluxing conditions gave 3-(benzofuran-2-yl)-5-(4-aryl)-4,5-dihydropyrazole-1-carbothioamides 4a,b. The pyrazolines 7a-d were synthesized by treating 4a,b with phenacyl bromides in refluxing ethanol. All the synthesized compounds were screened for their antibacterial and antifungal activities at 100 microg concentration. Some of our compounds showed excellent antimicrobial activities than control drugs.     

Synthesis and antiinflammatory activity of 4-amino-2-aryl-5-cyano-6-{3- and 4-(N-phthalimidophenyl)} pyrimidines

Six new 4-amino-5-cyano-2,6-diarylpyrimidines 5a-h has been synthesized in a facile manner by reacting the appropriate arylamidines 4a-d with bisnitriles 3a-e. Reduction of the nitro group of 5a-e using Pd in ethyl acetate furnished 6a-e in good yields. Reaction of 6a-e individually with phthalic anhydride yielded 7a-e in good to excellent yields. The newly synthesized heterocycles were characterized by IR, (1)H-NMR and mass spectral data. Compounds 5f-h and 7a-e were also evaluated against inflammation. Pyrimidines 5g, h exhibited better antiinflammatory activity when compared with acetylsalicylic acid (ASA). Phthalimide derivatives 7a-e also presented antiinflammatory activity, and three of them, viz., 7a-c have been found to be twice more active than aspirin. Cytotoxical evaluations of compounds 7a-e using neoplastic cells (NCI-H(292) and Hep-2) presented 41% of growth inhibition of neoplastic cells NCI-H(292).     

Syntheses and evaluation of 3-(3-bromo phenyl)-5-phenyl-1-(thiazolo [4,5-b] quinoxaline-2-yl)-2-pyrazoline derivatives

A variety of 3-(3-bromo phenyl)-5-phenyl-1-(thiazolo [4,5-b] quinoxaline-2-yl)-2-pyrazoline were obtained by the refluxing of 1-N-thiocarbamoyl 3,5-diphenyl-2-pyrazoline with 2,3-dichloroquinoxaline. The chemical structures of the compounds were elucidated by UV, IR, (1)H NMR, and (13)C NMR spectroscopy. The purity of the compounds was confirmed by their elemental analysis. The antiamoebic activity of these compounds was evaluated by microdilution method against HMI:IMSS strain of Entamoeba histolytica and the IC(50) values were compared with the standard drug metronidazole. Some of the quinoxaline derivatives showed less IC(50) values than metronidazole. To elucidate the toxic effect, MTT assay was performed using kidney epithelial cell line. The results showed that all the compounds are non-toxic.     

Inhibitory and bactericidal potential of crude acetone extracts of Combretum molle (Combretaceae) on drug-resistant strains of Helicobacter pylori

Infection with Helicobacter pylori is strongly associated with a number of gastroduodenal pathologies. Antimicrobial resistance to commonly-used drugs has generated a considerable interest in the search for novel therapeutic compounds from medicinal plants. As an ongoing effort of this search, the susceptibility of 32 clinical strains of H. pylori and a reference strain-NCTC 11,638-was evaluated against five solvent extracts of Combretum molle, a plant widely used for the treatment of gastric ulcers and other stomach-related morbidities in South Africa. The extracts were screened for activity by the agar-well diffusion method, and the most active one of them was tested against the same strains by micro-broth dilution and time kill assays. Metronidazole and amoxicillin were included in these experiments as positive control antibiotics. The solvent extracts all demonstrated anti-H. pylori activity with zone diameters of inhibition between 0 and 38 mm. The most potent anti-H. pylori activity was demonstrated by the acetone extract, to which 87.5% of the clinical strains were susceptible. The minimum inhibitory concentration (MIC90) values for this extract ranged from 1.25 to 5.0 mg/mL while those for amoxicillin and metronidazole ranged from 0.001 to 0.94 mg/mL and from 0.004 to 5.0 mg/mL respectively. The acetone extract was highly bactericidal at a concentration of 2.5 and 5.0 mg/mL, with complete elimination of the test organisms in 24 hours. Its inhibitory activity was better than that of metronidazole (p<0.05) as opposed to amoxicillin (p<0.05). The results demonstrate that C. molle may contain therapeutically-useful compounds against H. pylori, which are mostly concentrated in the acetone extract.     

Synthesis of new 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1,3-thiazolino[5,4-b]quinoxaline derivatives and evaluation of their antiamoebic activity

In an effort to develop potent antiamoebic agents, we have synthesized chalcones (1-8), amino-5-substituted-(3-phenyl(2-pyrazolinyl))methane-1-thione derivatives (1a-8a) and 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1,3-thiazolino[5,4-b]quinoxaline derivatives (1b-8b) and evaluated for their in vitro antiamoebic activity against HM1:IMSS strain of E. histolytica. All the compounds were characterized by electronic, IR, (1)H NMR and mass spectroscopic data. It was observed that the antiamoebic activity enhances on modifying the structure of chalcones to the pyrazolines and further to quinoxalines. The MTT assay was performed on human kidney epithelial cell line to check the cytotoxicity of the compounds and the results were compared with metronidazole. Compound 6b showed better antiamoebic activity and less toxicity than metronidazole.     

Crude ethanolic extracts of Garcinia kola seeds Heckel (Guttiferae) prolong the lag phase of Helicobacter pylori: inhibitory and bactericidal potential

Problems associated with current treatment regimens have generated a considerable interest in alternative approaches for the eradication of Helicobacter pylori infections using phytochemical compounds. In an attempt to identify potential sources of such compounds, the antimicrobial activity of five solvent extracts of Garcinia kola seeds were investigated against 30 clinical strains of H. pylori and a standard control strain, NCTC 11638, using standard microbiological techniques. Metronidazole and amoxicillin were included in these experiments as positive control antibiotics. All the extracts tested exhibited anti-H. pylori activity with zone diameters of inhibition between 0 and 25 mm. The ethanol extract demonstrated considerable anti-H. pylori activity with a percentage susceptibility of 53.3% and minimum inhibitory concentration for 50% susceptibility (MIC??) values ranging from 0.63 to 5.0 mg/mL. Ranges of MIC?? values for amoxicillin and metronidazole were 0.01-0.63 mg/mL and 0.04-5.0 mg/mL, respectively. The inhibitory activity of the ethanol extract was similar to that of metronidazole (P?>?.05) as opposed to amoxicillin (P?相似文献   

Synthesis, characterization and antibacterial activity of 2-[1-(5-chloro-2-methoxy-phenyl)-5-methyl-1H-pyrazol-4-yl]-5-(substituted-phenyl)-[1,3,4]oxadiazoles

In the present investigation a series of novel 2-[1-(5-chloro-2-methoxy-phenyl)-5-methyl-1H-pyrazol-4-yl]-5-(substituted-phenyl)-[1,3,4]oxadiazoles (4a–j) were synthesized by cyclization of substituted-benzoic acid N′-[1-(5-chloro-2-methoxy-phenyl)-5-methyl-1H-pyrazole-4-carbonyl]-hydrazide by using phosphorousoxychloride at 120 °C. The chemical structure of the newly synthesized compounds was characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR and LC–MS) methods. The title compounds were screened for qualitative (zone of inhibition) and quantitative antibacterial activity (MIC) by agar cup plate and microtitration methods, respectively. Among the synthesized compounds in this series compound 2-[1-(5-chloro-2-methoxyphenyl)-5-methyl-1H-pyrazol-4-yl]-5-(4-fluorophenyl)-1,3,4-oxadiazole (4b) was found to exhibit significant antibacterial activity with MICs of 22.4, 29.8, 29.6 and 30.0 μg/mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, respectively. The other compounds exhibited moderate activity when compared to standard substance Ampicillin.     

Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles and some related compounds

Two novel series of 4-thiazolidinone derivatives, namely 2-substituted-3-([4-(4-methoxybenzoylamino)benzoyl]amino)-4-thiazolidinones (7a-e) and 2-[4-(4-methoxybenzoylamino)benzoylhydrazono]-3-alkyl-4-thiazolidinones (5a-c) together with 2-[4-(4-methoxybenzoylamino)phenyl]-5-(substituted phenyl)amino-1,3,4-oxadiazoles (6a-c) have been synthesised as title compounds. N(1)-[4-(4-methoxybenzoylamino)benzoyl]-N(2)-substituted methylene hydrazines (3a-e) and 1-[4-(4-methoxybenzoylamino)benzoyl]-4-substituted phenyl thiosemicarbazides (4a-f) were also prepared and used as intermediate to give the title compounds. All synthesised compounds were screened for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv and antimicrobial activities against various bacteria and fungi. Compounds 7a and 7b were found as the most active derivatives demonstrating 90 and 98% inhibition of mycobacterial growth of M. tuberculosis H37Rv in the primary screen at 6.25 microg mL(-1), respectively. However, level II assay revealed that the MIC values were not less than 6.25 microg mL(-1). None of the compounds showed significant antimicrobial activity against the microorganisms used whereas 3a and 7a inhibited the growth of several bacteria and fungi.     

Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents

Four series of pyrazolyl benzenesulfonamide derivatives have been synthesized. The first series was prepared by cyclization of the intermediate N,N-dimethylaminomethylene-4[3-phenyl-4-(substituted thiosemicarbamoyl hydrazonomethyl)-1H-pyrazol-1-yl]benzenesulfonamide 2a-c with ethyl bromoacetate to afford the corresponding thiazolidinyl derivatives 3a-c. The second series was prepared by cyclization of the key intermediates 2a-c with 4-bromophenacyl bromide giving rise to thiazolinyl derivatives 4a-c. Thiadiazolyl derivatives 5a-c were obtained by heating 2a-c with 2M FeCl(3) solution. Refluxing the intermediates 2a-c in acetic anhydride yielded the corresponding thiadiazolinyl derivatives 6a-c. All the target compounds showed anti-inflammatory activity and three of them 3b, 3c and 4c surpassed that of indomethacin both locally and systemically in the cotton pellet granuloma and rat paw edema bioassay. The active compounds showed selective inhibitory activity towards COX-2 enzyme as revealed by the in vitro enzymatic assay. All the tested compounds proved to have superior gastrointestinal (GI) safety profiles as compared to indomethacin, when tested for their ulcerogenic effects. The acute toxicity study of compounds having promising anti-inflammatory activity (3b, 3c and 4c) indicated that they are well tolerated both orally and parenterally. Antimicrobial activity tests expressed as minimal inhibitory concentrations (MIC), revealed that compounds 3b and 4a showed comparable antibacterial activity to that of ampicillin against Escherichia coli, while compounds 3a, 3c and 4a possessed about half the activity of ampicillin against Staphylococcus aureus. On the other hand, the results showed that all the tested compounds have weak or no antifungal activity against Candida albicans except for compounds 6b and 6c that showed half the activity of the control antifungal drug used (clotrimazole).     

Stereoselective synthesis and QSAR study of cytotoxic 2-(4-oxo-thiazolidin-2-ylidene)-2-cyano-N-arylacetamides

(2Z,5Z) 2-[(5-Arylidene-4-oxo-3-phenyl)-thiazolidin-2-ylidine]-2-cyano-N-arylacetamides 4a-l were stereoselectively prepared via condensation of aromatic aldehydes with 4-thiazolidinones 3a-c. The latters were obtained via electrophilic attack of phenylisothiocyanate on 2-cyano-N-arylacetamides 1a-c followed by reaction with chloroacetyl chloride under basic condition. Single crystal X-ray study of 3a allows good confirmation for the assigned structure. Additionally, 5-arylhydrazono analogs 5a-e were prepared via condensation of the appropriate diazonium salts with 4-thiazolidinones 3a,b. Many of the synthesized compounds exhibited promising antitumor properties against colon HCT116, breast MCF7 and liver HEPG2 cell lines. 3D-Pharmacophore modeling and QSAR analysis were combined to explain the observed antitumor properties.     

Synthesis and antimicrobial studies of a new series of 2-[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]-5-substituted-1,3,4-oxadiazoles

A series of novel 2-[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]-5-substituted-1,3,4-oxadiazoles were synthesized by the oxidative cyclisation of hydrazones derived from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde and aroylhydrazines using chloramine-T as oxidant. IR, NMR and elemental analysis characterized the newly synthesized compounds. The synthesized compounds were evaluated for their antimicrobial activity and were compared with standard drugs. The compounds demonstrated potent to weak antimicrobial activity. Out of the compounds studied, compounds 8c and 8d showed significant inhibition. Compounds 8b, 8f, 8k and 8e showed moderate activity. The minimum inhibitory concentration of the compounds was in the range of 8-26 microg ml(-1) against bacteria and 8-24 microg ml(-1) against fungi. The title compounds represent a novel class of potent antimicrobial agents.     

Synthesis, molecular modeling and biological evaluation of 2-(benzylthio)-5-aryloxadiazole derivatives as anti-tumor agents

A series of 2-(benzylthio)-5-aryloxadiazole derivatives have been designed and synthesized, and their biological activities are also evaluated for EGFR inhibitory activity. Fourteen compounds among the twenty compounds are reported for the first time. Their chemical structures are characterized by (1)H NMR, MS, and elemental analysis. Anti-proliferative and EGFR inhibition assay results have demonstrated that compound 3e shows the most potent biological activity (IC(50)?=?1.09?μM for MCF-7 and IC(50)?=?1.51?μM for EGFR). Docking simulation has been performed to position compound 3e into the EGFR active site to determine the probable binding model, with an estimated binding free energy value of?-10.7?kcal/mol. Compound 3e with potent inhibitory activity in tumor growth inhibition may be a promising anti-tumor leading compound for the further research.     

Synthesis and in vitro selective anti-Helicobacter pylori activity of N-substituted-2-oxo-2H-1-benzopyran-3-carboxamides

In order to develop new anti-Helicobacter pylori agents, five new and three already known N-substituted-2-oxo-2H-1-benzopyran-3-carboxamides (coumarin-3-carboxamides) were prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. Among the prepared compounds those with a 4-acyl-phenyl group showed the best activity against H. pylori metronidazole resistant strains in the 0.25-1 microg/ml MIC range, indicating the presence of an acyl function as an important feature for activity.     

Synthesis and antimicrobial activities of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines carrying thioalkyl and sulphonyl phenoxy moieties

Thirty one new 6-aryl-3-{(4-substituted phenoxy) methyl}-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles (6a-s) and 6-aryl-3-[(4-substituted phenoxy methyl]-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (7a-l) have been synthesized from 4-thioalkyl phenols (1a-b) through a multi-step reaction sequence. Compounds 1a-b reacted with ethyl chloroacetate in presence of acetone and potassium carbonate to give ethyl [4-(thioalkyl) phenoxy] acetates (2a-b). Further, 2a was oxidized to [4-(methyl sulphonyl) phenoxy] acetate (2c) using hydrogen peroxide in acetic acid. Reactions of (2a-c) with hydrazine hydrate in alcoholic medium furnished 2-[4-thiosubstituted phenoxy] acetohydrazides (3a-b) and 2-[4-methyl sulphonyl phenoxy] acetohydrazide (3c) which on treatment with carbon disulphide and methanolic potassium hydroxide yielded corresponding potassium dithiocarbazates (4a-c). They were then converted to 4-amino-5-[(4-thioalkyl phenoxy) methyl]-4H-1,2,4-triazole-3-thiols (5a-b) and 4-amino-5-[(4-methyl sulphonyl phenoxy) methyl]-4H-1,2,4-triazole-3-thiol (5c) by refluxing them with aqueous hydrazine hydrate. The title compounds 6a-s were prepared by condensing 5a-c with various aromatic carboxylic acids in presence of phosphorus oxychloride. The intermediates 5a-c, on condensation with various substituted phenacyl bromides afforded a series of title compounds (7a-l). The structures of new compounds 2a-7l were established on the basis of their elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. All the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against three fungi. Preliminary results indicate that some of them exhibited promising activities and they deserve more consideration as potential antimicrobials.     

Synthesis and antileishmanial activity of novel 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituents

In order to optimize the antileishmanial activity of piperazinyl-linked 5-(5-nitrofuran-2-yl)-1,3,4-thiadiazoles, we synthesized a series of 5-(5-nitrofuran-2-y1)-1,3,4-thiadiazoles with piperazinyl-linked benzamidine substituent as scaffold found in pentamidine related antiprotozoals. The structure of target compounds was confirmed by IR, 1H NMR, 13C NMR and Mass spectral data. All compounds were tested for in vitro activity against the promastigote and amastigote forms of Leishmania major. From the results, we found that the substitution on amidine nitrogen has profound role in the biological activity of these compounds. The 5-nitrofuran-2-yl-1,3,4-thiadiazoles having n-propyl, n-butyl and benzyl side chain on benzamidine (as in compounds 2d, 2e and 2g, respectively) showed very good activity in both forms of promastigote and amastigote. The most active compound was N-propyl-4-(4-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-yl)piperazin-1-yl) benzamidine hydrochloride (2d) with IC50 value of 0.08 μM in promastigote model. This compound showed a very low level of toxicity against macrophages (CC50=785 μM), with the highest selectivity index (SI=78.5) among the tested compounds.     

Synthesis, anticonvulsant activity and 5-HT1A, 5-HT2A receptor affinity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione

The synthesis, physicochemical and pharmacological properties of new N-[(4-arylpiperazin-1-yl)-alkyl]-2-azaspiro[4.4]nonane- (8a-c, 10a-d) and [4.5]decane-1,3-dione (9a-c, 11a-d) derivatives were described. The antiepileptic effects of those compounds were examined by a maximal electroshock (MES) and a pentylenetetrazole (sc. PTZ) tests, and their neurotoxicity was determined using a rota-rod test. Compounds 8c, 9c, 10c, d, 11c, d with a CF(3) group at the 3-position of the 4-arylpiperazine fragment exhibited anti-seizure properties in the MES model; in contrast, their 2-CH(3) and 2-OCH(3) analogues were inactive in both the tests used. Moreover, since the investigated compounds belong to the class of long-chain arylpiperazines, their serotonin 5-HT(1A) and 5-HT(2A) receptor affinity was determined. The relationship between the length of alkylene spacer and 5-HT(1A)/5-HT(2A) receptor activity was observed. Compounds with an ethylene and a propylene bridge (10a-d and 11a-d) were 3-80-fold more potent (K(i) ranged from 3.1 to 94 nM for 5-HT(1A) and 32-465 nM for 5-HT(2A)) than their methylene analogues (8a-c and 9a-c; K(i) ranged from 81 to 370 nM for 5-HT(1A) and 126-1370 nM for 5-HT(2A)). The highest 5-HT(1A) receptor affinity was displayed by 2-OCH(3) and 3-CF(3) phenyl derivatives (10b, 11b: K(i)=6.8 and 5.7 nM, respectively, and 10c, 11c: K(i)=6.0 and 3.1 nM, respectively), while in the case of 5-HT(2A) receptor the highest affinity was observed for the 3-CF(3) phenyl derivatives 10c, d, 11c, d (K(i) ranged from 32 to 86 nM).     

Synthesis and preliminary evaluation of some N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones as antimicrobial agents

Two series of N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide (4a-m) and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones (5a-m) were synthesised using appropriate synthetic route. All the test compounds 4a-m and 5a-m were assayed in vitro for antibacterial activity against two different strains of Gram-negative (Escherichia coli and S. typhi) and Gram-positive (S. aureus, B. subtilis) bacteria and the antimycobacterial activity was evaluated against M. tuberculosis and M. avium strains. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. The test compounds have shown significant antibacterial and antimycobacterial activity against all the microbial strains used, when tested in vitro. In general, along with the thienopyrimidinone ring, substituted amido or imino side chain at position 3 is essential for antimicrobial activity. Among the compounds tested, compounds 4c, 4e and 4g in N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide series and compounds 5c, 5e and 5g in 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones series were found to be the most potent. Further the toxicity of most potent compounds 4c, 4e and 4g and 5c, 5e and 5g were assessed using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. In general, test compounds were found to be non-toxic up to a dose level of 200 micromol L(-1) (MHC).     

In vivo antitumor, in vitro antibacterial activity and alkylating properties of phosphorohydrazine derivatives of coumarin and chromone

The aim of this research was to examine chemical and biological properties of the products (4a-c/5a-c, 8b-c, 9a-b) of the reaction of methyl chromone-3-carboxylate (2), 3-formyl-4-hydroxycoumarin (3), 3-formylchromone (6) and chromone 3-carbonyl chloride (7) with phosphorus hydrazides (1a-c). For structure and keto-enol tautomerism analyses (1)H, (13)C, (31)P NMR spectroscopy was used. The ring transformation species (4a-c/5a-c) containing the coumarin ring (5a-c) were predominant in the solution. The chromone series 8b-c and 9a-b was obtained in reaction of phosphorus hydrazides (1a-c) with 3-formylchromone (6) and chromone-3-carbonyl chloride (7). Alkylating activity of phosphorohydrazides of coumarin and chromone was determined with in vitro Preussmann test (NBP test). Some of the compounds were examined towards antitumor and antibacterial activity. Compounds 4b-c/5b-c and 9a demonstrated in vitro antitumor activity against P388 leukemia. Antineoplastic activity of the compounds 4b/5b and 9a combined with methotrexate was showed using L1210 murine leukemia.