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1.
Agarwal A Ramesh Ashutosh Goyal N Chauhan PM Gupta S 《Bioorganic & medicinal chemistry》2005,13(24):6678-6684
A series of dihydropyrido[2,3-d]pyrimidines have been synthesized and screened for its in vitro antileishmanial activity profile in promastigote and amastigote models. Compounds 2a-2l have shown 83-100% inhibition against promastigotes and 79-100% inhibition against amastigotes at a concentration of 50 microg/mL. 相似文献
2.
Shikha S. Chauhan Leena Gupta Monika Mittal Preeti Vishwakarma Suman Gupta Prem M.S. Chauhan 《Bioorganic & medicinal chemistry letters》2010,20(21):6191-6194
A series of indolylglyoxylamide derivatives have been synthesized and evaluated in vitro against amastigote form of Leishmania donovani. Compound 8c has been identified as the most active analog of the series with IC50 value of 5.17 μM and SI value of 31.48, and is several folds more potent than the standard drugs sodium stilbogluconate and pentamidine. 相似文献
3.
Nagarapu Srinivas Shraddha Palne Suman Gupta Kalpana Bhandari 《Bioorganic & medicinal chemistry letters》2009,19(2):324-327
Thirteen novel aryloxy cyclohexane-based mono and bis imidazoles were synthesized and evaluated in vitro as antileishmanials against Leishmania donovani and cytotoxicity assessed. These compounds were better than the existing drugs, sodium stibogluconate and pentamidine in respect to IC50 and SI values. Promising compounds were tested further in vivo. Among all, the bis methylimidazole with 2-fluoro, 4-nitro aryloxy group (9) exhibited significant in vivo inhibition of 77.9%, thus providing new structural lead for antileishmanials. 相似文献
4.
We report new organoselenium compounds bearing the sulfonamide moiety as effective inhibitors of the β-isoform of Carbonic Anhydrase from the unicellular parasitic protozoan L. donovani chagasi. All derivatives were evaluated in vitro for their leishmanicidal activities against Leishmania infantum amastigotes along with their cytotoxicities in human THP-1 cells. Compounds 3e-g showed their activity in the low micromolar range with IC50 values spanning from 0.72 to 0.81 µM and selectivity indexes (SI) > 8 (for 3g SI > 30), thus much higher than those observed for the reference drugs miltefosine and edelfosine. This is the first study which reports new selenoderivatives with promising leishmanicidal properties and acting as Carbonic Anhydrase inhibitors too thus paving the way to the development of innovative agents for the treatment of neglected diseases such as leishmaniasis. 相似文献
5.
Clark RL Carter KC Mullen AB Coxon GD Owusu-Dapaah G McFarlane E Duong Thi MD Grant MH Tettey JN Mackay SP 《Bioorganic & medicinal chemistry letters》2007,17(3):624-627
The continual increase in drug resistance; the lack of new chemotherapeutic agents; the toxicity of existing agents and the increasing morbidity with HIV co-infection mean the search for new antileishmanial agents has never been more urgent. We have identified the benzodiazepines as a structural class for antileishmanial hit optimisation, and demonstrated that their in vitro activity is comparable with the clinically used drug, sodium stibogluconate, and that the compounds are not toxic to macrophages. 相似文献
6.
《Bioorganic & medicinal chemistry》2014,22(15):4018-4027
A new series of triazolopyridyl pyridyl ketones has been synthetized by regioselective lithiation of the corresponding [1,2,3]triazolo[1,5-a]pyridine at 7 position followed by reaction with different electrophiles. The in vitro antileishmanial activity of these compounds was evaluated against Leishmania infantum, Leishmania braziliensis, Leishmania guyanensis and Leishmania amazonensis. Compounds 6 and 7 were found to be the most active leishmanicidal agents. Both of them showed activities at micromolar concentration against cultured promastigotes of Leishmania spp. (IC50 = 99.8–26.8 μM), without cytotoxicity on J774 macrophage cells. These two compounds were also tested in vivo in a murine model of acute infection by L. infantum. The triazolopyridine derivative 6 was effective against both spleen and liver parasites forms, while 7 was inactive against liver parasites. Mechanistic aspects of the antileishmanial activity were investigated by means of DNA binding studies (UV-titration and viscosimetry). Results have revealed that these active ligands are able to interact strongly with DNA [Kb = 1.14 × 105 M−1 (6) and 3.26 × 105 M−1 (7)]. Moreover, a DNA groove binding has been proposed for both 6 and 7. To provide more insight on the mode of action of compounds 6 and 7 under biological conditions, their interaction with bovine serum albumin (BSA) was monitored by fluorescence titrations and UV–visible spectroscopy. The quenching constants and binding parameters were determined. Triazolopyridine ketones 6 and 7 have exhibited significant affinity towards BSA [Kb = 2.5 × 104 M−1 (6) and 1.9 × 104 M−1 (7)]. Finally, to identify the binding location of compounds 6 and 7 on the BSA, competitive binding experiments were carried out, using warfarin, a characteristic marker for site I, and ibuprofen as one for site II. Results derived from these studies have indicated that both compounds interact at BSA site I and, to a lesser extent, at site II. 相似文献
7.
Panda G Shagufta Mishra JK Chaturvedi V Srivastava AK Srivastava R Srivastava BS 《Bioorganic & medicinal chemistry》2004,12(20):5269-5276
A new series of diaryloxy methano phenanthrenes were prepared through tertiary-aminoalkylations of [(methoxy-phenyl)-phenanthren-9-yl-methyl]-phenols obtained from Friedel-Crafts alkylations on (methoxy-phenyl)-phenanthren-9-yl-methanols. These series of compounds were evaluated against Mycobacterium tuberculosis H37Rv and showed the desired activity in the range of 6.25 microg/mL in vitro. One of the compound 12j protects the mice from the challenge of M. tuberculosis in vivo, as 30% of the mice were survived at treatment of 50 mg/kg body weight. 相似文献
8.
Khatik GL Kaur J Kumar V Tikoo K Nair VA 《Bioorganic & medicinal chemistry letters》2012,22(5):1912-1916
Sulfide and sulfonyl derivatives of 1,2,4-oxadiazoles were synthesized and screened by MTT assay on the prostate cancer cells, DU-145. Six compounds were identified as potential anti-prostate cancer agents with IC(50) values ranging from 0.5 to 5.1μM. These compounds exhibited good activity on the androgen independent cells PC-3, while the results were moderate on androgen dependent LNCaP cells, suggesting the possibility of a mechanism of action different from that of the bioisosteric bicalutamide. Also a very low cytotoxicity was observed on non-cancerous cells MCF-10A. 相似文献
9.
Ashutosh Kumar Akihiro Ito Mikako Hirohama Minoru Yoshida Kam Y.J. Zhang 《Bioorganic & medicinal chemistry letters》2013,23(18):5145-5149
SUMO activating enzyme 1 (SUMO E1) is the first enzyme in sumoylation pathway and an important cancer drug target. However, only a few inhibitors were reported up to now that includes three natural products, semi-synthetic protein inhibitors and one AMP mimic. Here, we report the identification of quinazolinyloxy biaryl urea as a new class of SUMO E1 inhibitors. The most active compound of this class inhibited the in vitro sumoylation with an IC50 of 13.4 μM. This compound inhibits sumoylation by blocking the formation of SUMOE1-SUMO thioester intermediate. The biological activity of the most active compound is comparable to previously reported inhibitors with properties suitable for medicinal chemistry optimization for potency and druggability. 相似文献
10.
Hu L Arafa RK Ismail MA Wenzler T Brun R Munde M Wilson WD Nzimiro S Samyesudhas S Werbovetz KA Boykin DW 《Bioorganic & medicinal chemistry letters》2008,18(1):247-251
Eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave IC50 values less than 1 microM, five exhibited values less than 0.40 microM, and two gave values less than 0.10 microM in a Leishmania donovani axenic amastigote assay. The activity of the diamidines strongly depends on the ring N-atom location relative to the amidine groups and correlates with DNA affinity. Transmission electron microscopy studies showed a dramatic dilation of the mitochondrion and evidence of disintegration of the kinetoplast of the amastigotes. 相似文献
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12.
Gupta L Talwar A Nishi Palne S Gupta S Chauhan PM 《Bioorganic & medicinal chemistry letters》2007,17(14):4075-4079
A series of marine alkaloid 8,9-dihydrocoscinamide B, its analogues and indolylglyoxylamide derivatives have been synthesized and screened for their in vitro antileishmanial activity profile in promastigote and amastigote models. Compounds 7 and 10 have shown 99-100% inhibition against promastigotes and 97-98% inhibition against amastigotes at a concentration of 10 microg/ml. 相似文献
13.
Chloropyrimidines as a new class of antimicrobial agents 总被引:1,自引:0,他引:1
Agarwal N Srivastava P Raghuwanshi SK Upadhyay DN Sinha S Shukla PK Ji Ram V 《Bioorganic & medicinal chemistry》2002,10(4):869-874
In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 microg/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 microg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 microg/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes. 相似文献
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15.
Cena C Boschi D Tron GC Chegaev K Lazzarato L Di Stilo A Aragno M Fruttero R Gasco A 《Bioorganic & medicinal chemistry letters》2004,14(24):5971-5974
A new class of NO-donor phenol derivatives is described. The products were obtained by joining appropriate phenols with either nitrooxy or 3-phenylsulfonylfuroxan-4-yloxy moieties. All the compounds proved to inhibit the ferrous salt/ascorbate induced lipidic peroxidation of membrane lipids of rat hepatocytes. They were also capable of dilating rat aorta strips precontracted with phenylephrine. 相似文献
16.
As a part of our project aimed at developing new safe chemotherapeutic agents against tropical diseases, a series of aryl derivatives of 2- and 3-aminoquinoline, some of them new compounds, was designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the parasite responsible for American trypanosomiasis (Chagas’ disease), and Leishmania mexicana, the etiological agent of Leishmaniasis. Some of them showed a remarkable activity as parasite growth inhibitors. Fluorine-containing derivatives 11b and 11c were more than twice more potent than geneticin against intracellular promastigote form of Leishmania mexicana exhibiting both IC50 values of 41.9 μM. The IC50 values corresponding to fluorine and chlorine derivatives 11b–d were in the same order than benznidazole against epimastigote form. These drugs are interesting examples of effective antiparasitic agents with outstanding potential not only as lead drugs but also to be used for further in vivo studies. In addition, the obtained compounds showed no toxicity in Vero cells, which makes them good candidates to control tropical diseases. Regarding the probable mode of action, assayed quinoline derivatives interacted with hemin, inhibiting its degradation and generating oxidative stress that is not counteracted by the antioxidant defense system of the parasite. 相似文献
17.
A new class of therapeutic agents, sharing inhibition of the slow calcium channel, will soon be available to the American patient. Selective action of these agents upon the atrioventricular node, the smooth muscle of coronary and peripheral arteries, and the contractility of cardiac muscle opens new vistas in cardiovascular pharmacology. Early release of these agents by the Federal Drug Administration for general use is urged, based upon the already wide and successful experience in the European and South American continents. 相似文献
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19.
Amit R. Trivedi Vimal R. Bhuva Bipin H. Dholariya Dipti K. Dodiya Vipul B. Kataria Viresh H. Shah 《Bioorganic & medicinal chemistry letters》2010,20(20):6100-6102
A small library of 30 dihydropyrimidines was synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. Two compounds, ethyl 4-[3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxylate 4a and ethyl 4-[3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl]-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 4d were found to be the most active compounds in vitro with MIC of 0.02 μg/mL against MTB and were more potent than isoniazid. 相似文献
20.
Gnoatto SC Dalla Vechia L Lencina CL Dassonville-Klimpt A Da Nascimento S Mossalayi D Guillon J Gosmann G Sonnet P 《Journal of enzyme inhibition and medicinal chemistry》2008,23(5):604-610
A series of new ursolic and oleanolic acids derivatives was synthesized via ursolic or oleanolic acids, previously extracted from South American Ilex species. These new compounds were tested for in vitro antiparasitic activity on Leishmania amazonensis and Leishmania infantum strains. Some of these compounds showed activity against the promastigote forms of L. amazonensis or L. infantum, with IC(50) ranging from 5 to 12 microM. As expected, most of the compounds showed a significant level of cytotoxicity against monocytes (IC(50) = 2-50 microM). From a structure-activity relationships point of view, these pharmacological results enlightened mainly the importance of an acetylation at position 3 of the oleanolic acid skeleton in the activity against the L. amazonensis strain, and of a bis-(3-aminopropyl)piperazine moiety on the carboxylic function of ursolic acid against the L. infantum strain. 相似文献