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1.
Badri Narayan Acharya Deepika Saraswat Mahabir Parshad Kaushik 《Medicinal chemistry research》2008,17(8):530-540
Abstract Antimalarial efficacy of Gomphostemma crinitum leaf extracts were studied in vitro against the chloroquine-sensitive MRC-02 strain of Plasmodium falciparum. The CHCl3 extract (IC50 37.28 μg/mL) was found to be better than the aqueous extract (IC50 111.4 μg/mL). The major compound present in CHCl3 extract was coded as GC-7 (12,17-diacetoxy, 15-hydroxy, 2-oxo, 3, 13 E (14)-diene clerodane). Seasonal variation of GC-7 was studied and correlated to the antimalarial efficacy of the crude extracts
of leaves collected in different months. GC-7 was found to be the only regular compound present in G.
crinitum leaves throughout the year. A good correlation between antimalarial efficacy (IC50 9.3 μg/mL) and concentration of GC-7 in crude extracts was observed. The mode of action of GC-7 was found to be different
from that of chloroquine.
Graphical Abstract Antimalarial activity of Gomphostemma crinitum leaf extracts
B.N Acharya, Deepika Saraswat and M.P Kaushik*
Discovery Centre, Process Technology Development Division
Defence R & D Establishment, Jhansi Road, Gwalior-474002 (MP) INDIA
#Entomology division, Defence Research and Development Establishment,Gwalior-474002, India
Antimalarial activity of chloroform extract of G. crinitum leaves and an isolated compound GC-7 (12,17-diacetoxy,15-hydroxy,2-oxo,3,13 E (14)-diene clerodane) against a chloroquine susceptible strain of Plasmodium falciparum is described. 相似文献
2.
Abstract With the aim of developing potential antifungals, a series of chalcones incorporating sulfur either as part of a heteroaromatic
ring (thiophene) or as a side chain (thiomethyl group) were synthesized and tested for their in vitro activity. Some of the
compounds showed appreciable activity against a fluconazole-resistant strain, and could act as new hits for the design of
better analogs.
Graphical Abstract Synthesis and biological evaluation of α,β-unsaturated ketone as potential antifungal agentsSeema Bag, S.Ramar, Mariam S.
Degani*With an aim to develop new chemical entities with potent antifungal activity against Candida albicans strains, a series of chalcones incorporating sulfur either as part of a heteroaromatic ring (thiophene) or as a side chain
(thiomethyl group) were synthesized.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
3.
Satish K. Awasthi Nidhi Mishra Brajesh Kumar Manish Sharma Amit Bhattacharya Lokesh C. Mishra Virendra K. Bhasin 《Medicinal chemistry research》2009,18(6):407-420
Abstract Several new chalcone analogues were synthesized and evaluated as inhibitors of malaria parasite. Inhibitory activity was
determined in vitro against a chloroquine-sensitive Plasmodium falciparum strain of parasites. The compound 3-(4-methoxyphenyl)-1-(4-pyrrol-1-yl-phenyl)prop-2-en-1-one was found to be the most active
with 50% inhibition concentration (IC50) of 1.61 μg/ml. This inhibitory concentration is comparable to a prototype phytochemical chalcone, licochalcone A, with an
IC50 of 1.43 μg/ml. The present study suggests that small, lipophilic nitrogen heterocyclic ring A together with small hydrophobic
functionality at ring B can enhance antimalarial activity. These results suggest that chalcones are a class of compounds that
provides an option of developing inexpensive, synthetic therapeutic antimalarial agents in the future.
Graphical Abstract Claisen-Schmidt condensation method was employed to synthesize various substituted chalcones. Among all, 3-(4-Methoxyphenyl)-1-(4-pyrrol-1-yl-phenyl)prop-2-en-1-one
was found to be most effective with IC50 value of 1.6 μg/ml in vitro against chloroquine sensitive strain (3D7) of Plasmodium falciparum.
相似文献
4.
Núbia Boechat Maria de Lourdes G. Ferreira Luiz C. S. Pinheiro Antônio M. L. Jesus Milene M. M. Leite Carlos C. S. Júnior Anna C. C. Aguiar Isabel M. de Andrade Antoniana U. Krettli 《Chemical biology & drug design》2014,84(3):325-332
Malaria is one of the most prevalent parasitic diseases in the world. The global importance of this disease, current vector control limitations, and the absence of an effective vaccine make the use of therapeutic antimalarial drugs the main strategy to control malaria. Chloroquine is a cost‐effective antimalarial drug with a relatively robust safety profile, or therapeutic index. However, chloroquine is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of chloroquine‐resistant strains, which have also been reported for Plasmodium vivax. However, the activity of 1,2,3‐triazole derivatives against chloroquine‐sensitive and chloroquine‐resistant strains of P. falciparum has been reported in the literature. To enhance the anti‐P. falciparum activity of quinoline derivatives, we synthesized 11 new quinoline‐1H‐1,2,3‐triazole hybrids with different substituents in the 4‐positions of the 1H‐1,2,3‐triazole ring, which were assayed against the W2‐chloroquine‐resistant P. falciparum clone. Six compounds exhibited activity against the P. falciparum W2 clone, chloroquine‐resistant, with IC50 values ranging from 1.4 to 46 μm . None of these compounds was toxic to a normal monkey kidney cell line, thus exhibiting good selectivity indexes, as high 351 for one compound ( 11 ). 相似文献
5.
A. Samzadeh-Kermani H. Shafaroodi R. Miri H. Mirkhani M. Vosooghi A. Shafiee 《Medicinal chemistry research》2009,18(2):112-126
Abstract A series of alkyl, cycloalkyl, and aryl esters of nifedipine in which the o-nitrophenyl group at position 4 is replaced by 2-(4-chlorophenyl)-4-thiazolyl substituent were synthesized and evaluated
for their calcium channel antagonist activities using isolated ileum of guinea pig. The anticonvulsant activity of test drugs
was also assessed in pentylenetetrazole (PTZ)-induced seizure in male Naval Medical Research Institute (NMRI) mice model.
The results showed that although all compounds were at least 100 times less active than the reference drug nifedipine in terms
of calcium channel antagonist activity, nevertheless all compounds showed considerable anticonvulsant activity.
Graphical Abstract A new series of alkyl, cycloalkyl and aryl substituted 4-chlorophenylthiazolyl–1,4-dihydropyridines were synthesized and tested
for calcium channel inhibitory and anticonvulsant activities.
相似文献
6.
Shalini Sumit Kumar Mathieu Gendrot Isabelle Fonta Joel Mosnier Nosipho Cele Paul Awolade Parvesh Singh Bruno Pradines Vipan Kumar 《ACS medicinal chemistry letters》2020,11(12):2544
A series of amide tethered 4-aminoquinoline-naphthalimide hybrids has been synthesized to assess their in vitro antiplasmodial potential against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. The most active and noncytotoxic compound had an IC50 value of 0.07 μM against W2 strain and was more active than standard antimalarial drugs, including chloroquine, desethylamodiaquine, and quinine, particularly for drug resistant malaria. The promising scaffold, when subjected to heme binding and molecular modeling studies, was identified as a possible potent inhibitor of hemozoin formation and P. falciparum chloroquine resistance transporter (PfCRT), respectively, and, therefore, could act as a dual function antiplasmodial. 相似文献
7.
Amelia Puteri Nugroho Alfarius Eko Hirasawa Yusuke Kaneda Toshio Tougan Takahiro Horii Toshihiro Morita Hiroshi 《Journal of natural medicines》2021,75(3):633-642
Two new bisindole alkaloids, bisnaecarpamines A (1) and B (2), possessing a vobasine-sarpagine type skeleton were isolated from the bark of Tabernaemontana macrocarpa Jack. Their structures were elucidated by extensive spectroscopic methods and chemical correlation. The absolute configurations of compounds 1 and 2 were established using TDDFT-ECD calculation of the selected isomers. Bisnaecarpamine A exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 28.8 µM.
Graphic abstract8.
Pharmacophore hypotheses were developed for molecules having antimalarial activities targeting the haem detoxification pathway
of the malaria parasite. A training set consisting of 23 compounds was selected to generate these hypotheses, and their activities
were evaluated for haem polymerization inhibition and against chloroquine-sensitive (3D7) as well as chloroquine-resistant
(K1) strains of p. falciparum. The models were cross-validated by Fischer’s randomization test at a 95% confidence level. The model developed against chloroquine-resistant
malaria parasites was found to yield the best predictions among the three models. 相似文献
9.
Synthesis,Docking, In Vitro and In Vivo Antimalarial Activity of Hybrid 4‐aminoquinoline–1,3,5‐triazine Derivatives Against Wild and Mutant Malaria Parasites
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Hans Raj Bhat Udaya Pratap Singh Prashant Gahtori Surajit Kumar Ghosh Kabita Gogoi Anil Prakash Ramendra K. Singh 《Chemical biology & drug design》2015,86(3):265-271
A new series of hybrid 4‐aminoquinoline–1,3,5‐triazine derivatives was synthesized by a four‐step reaction. Target compounds were screened for in vitro antimalarial activity against chloroquine‐sensitive (3D‐7) and chloroquine‐resistant (RKL‐2) strains of Plasmodium falciparum. Compounds exhibited, by and large, good antimalarial activity against the resistant strain, while two of them, that is 8g and 8a, displayed higher activity against both the strains of P. falciparum. Additionally, docking study was performed on both wild (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) type pf‐DHFR‐TS to highlight the structural features of hybrid molecules. 相似文献
10.
11.
M. Gopalakrishnan J. Thanusu V. Kanagarajan R. Govindaraju 《Medicinal chemistry research》2009,18(5):341-350
Abstract A collection of biolabile (E)-1-(4-morpholinophenyl)-3-aryl-prop-2-en-1-ones 8–13 are synthesized, characterized by melting point, elemental analysis, mass spectroscopy (MS), Fourier-transform infrared (FT-IR),
and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic data and evaluated for their in vitro antibacterial and antifungal activities.
Compounds 8–13 exerted a wide range of antibacterial activities against all tested Gram-positive and Gram-negative bacterial strains. All
the compounds 8–13 were more active against Pseudomonas. Of the synthesized compounds, compounds 9 and 11 exhibited a wide range of antibacterial activities against Staphylococcus aureus, β-Heamolytic streptococcus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas. Compounds 10, 12, and 13 exerted strong antifungal activities against all tested fungal strains, namely Aspergillus flavus, Mucor, Rhizopus, and Microsporum gypsuem.
Graphical Abstract
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12.
Design,synthesis and in vitro antiplasmodial activity of some bisquinolines against chloroquine‐resistant strain
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Srinivasarao Kondaparla Pooja Agarwal Kumkum Srivastava Sunil K. Puri Seturam B. Katti 《Chemical biology & drug design》2017,89(6):901-906
A series of novel bisquinoline compounds comprising N1‐(7‐chloroquinolin‐4‐yl) ethane‐1,2‐diamine and 7‐chloro‐N‐(2‐(piperazin‐1‐yl)ethyl)quinolin‐4‐amine connected with 7‐chloro‐4‐aminoquinoline containing various amino acids is described. We have bio‐evaluated the compounds against both chloroquine‐sensitive (3D7) and chloroquine‐resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8‐ and 10.6‐fold superior activity as compared to chloroquine (CQ; IC50 = 0.255 ± 0.049 μm ) against the K1 strain with IC50 values 0.137 ± 0.014 and 0.026 ± 0.007 μm , respectively. Furthermore, compound 7 also displayed promising activity against the 3D7 strain (IC50 = 0.024 ± 0.003 μm ) of P. falciparum when compared to CQ. All the compounds in the series displayed resistance factor between 0.57 and 4.71 as against 51 for CQ. These results suggest that bisquinolines can be explored for further development as new antimalarial agents active against chloroquine‐resistant P. falciparum. 相似文献
13.
14.
15.
Romina J. Ronchi Claire Beaufay Joanne Bero Juan B. Robirosa Marcia Mazzuca Jorge A. Palermo Joëlle Quetin‐Leclercq Marianela Snchez 《Chemical biology & drug design》2019,93(2):147-153
In the present study, a series of new esters of secochiliolide acid (SA), a diterpene isolated from Nardophyllum bryoides, were synthesized in good yield. All compounds were evaluated for their in vitro antiparasitic properties (on Plasmodium falciparum and Trypanosoma brucei brucei) and cytotoxicity (on WI38, normal mammalian cells). They displayed moderate antitrypanosomal activity with IC50 values between 2.55 and 18.14 μm , with selectivity indices >10, and low antiplasmodial effects with IC50 > 29 μm . The only exception was the n‐hexyl ester of SA, which showed a strong and selective antiplasmodial activity (IC50 = 1.99 μm and selectivity index = 117.0). The in vivo antimalarial efficacy of this compound was then assessed according to the 4‐day suppressive test of Peters in mice. An intraperitoneal treatment at 50 mg kg?1 day?1 induced a slight parasitaemia reduction by 56% which was statistically significant on day 4 post‐infection and an increase in the survival time. 相似文献
16.
Raghu Raj Christophe Biot Séverine Carrère‐Kremer Laurent Kremer Yann Guérardel Jiri Gut Philip J. Rosenthal Delphine Forge Vipan Kumar 《Chemical biology & drug design》2014,83(5):622-629
A series of twenty piperazine‐tethered 7‐chloroquinoline–isatin hybrids have been synthesized via either direct nucleophilic substitution or Cu(Ι)Cl‐mediated Mannich reaction. These new conjugates were evaluated for their antimalarial and antitubercular efficacy against a chloroquine‐resistant strain of Plasmodium falciparum and Mycobacterium tuberculosis, respectively, while the cytotoxic profiles were evaluated against 3T6 cell line, a permanent mouse embryonic fibroblast cell line. The most potent of the test compound with IC50 of 0.22 μm against W2 strain of P. falciparum and 31.62 μm against the embryonic fibroblast cell line (cytotoxicity) displayed a high selective index of 143.73. 相似文献
17.
In the present study the chemopreventive effects of water soluble AquaROX® 15 and oil soluble VivOX® 40 rosemary extracts against 4-nitroquinoline-N-oxide (NQNO) and 2-amino-3-methyl-3H-imidazo[4,5-F]quinoline (IQ) induced mutagenicity in the reverse mutation assays with Salmonella typhimurium TA98 and against t-butyl hydroperoxide (t-BOOH), benzo(a)pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced DNA damage in HepG2 cells were studied, applying the comet assay. The results showed comparable protective effect of AquaROX and VivOX against oxidative DNA damage, whereas protection against indirect active genotoxic carcinogens was more efficient by VivOX. 相似文献
18.
Khaomek P Ichino C Ishiyama A Sekiguchi H Namatame M Ruangrungsi N Saifah E Kiyohara H Otoguro K Omura S Yamada H 《Journal of natural medicines》2008,62(2):217-220
Ethyl acetate (EtOAc) extract from the stem bark of Erythrina fusca showed a antimalarial activity against the multi-drug-resistant strain (K1) of Plasmodium falciparum, and six flavonoids, lupinifolin (1), citflavanone (2), erythrisenegalone (3), lonchocarpol A (4), liquiritigenin (5), and 8-prenyldaidzein (6), were isolated from the extract. Diprenylated flavanone 4 showed a notable antimalarial activity (IC50; 1.6 μg/mL); however 1 and 3 did not show the activity, even though these compounds possessed prenylated substitution. 相似文献
19.
Jian Xue Jiasheng Diao Guobin Cai Lisheng Deng Baisong Zheng Yuan Yao Yongcheng Song 《ACS medicinal chemistry letters》2013,4(2):278-282
d-xylulose-5-phosphate reductoisomerase
(DXR)
in the nonmevalonate isoprene biosynthesis pathway is a target for
developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor,
showed safety as well as efficacy against Plasmodium falciparum malaria in clinical trials. On the basis of our previous quantitative
structure–activity relationship (QSAR) and crystallographic
studies, several novel pyridine-containing fosmidomycin derivatives
were designed, synthesized, and found to be highly potent inhibitors
of P. falciparum DXR (PfDXR) having Ki values of 1.9–13 nM, with the best
one being ∼11× more active than fosmidomycin. These compounds
also potently block the proliferation of multidrug resistant P. falciparum with EC50 values as low as 170
nM. A 2.3 Å crystal structure of PfDXR in complex
with one of the inhibitors is reported, showing that the flexible
loop of the protein undergoes conformational changes upon ligand binding
and a hydrogen bond and favorable hydrophobic interactions between
the pyridine group and the PfDXR account for the
enhanced activity. 相似文献
20.
Antimalarial Effect of 3‐Methoxy‐1,2‐Dioxetanes on the Erythrocytic Cycle of Plasmodium falciparum
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Nicolas S. Lopes Ariane M. Yoshitake Adriana F. Silva Vani X. Oliveira Jr Leandro S. Silva Ana A. S. Pinheiro Luiz Francisco M. L. Ciscato 《Chemical biology & drug design》2015,86(6):1373-1377
The antimalarial activity of peroxides most likely originates from their interaction with iron(II) species located inside the malaria parasite, which forms destructive radical species through a Fenton‐like mechanism. This article reports the first evaluation of the in vitro antimalarial activity of three peroxides of the class 1,2‐dioxetanes against Plasmodium falciparum; the results reveal that the studied 3‐methoxy‐1,2‐dioxetanes display significant antimalarial activity, at a similar level as artemisinin and also that their reactivity toward iron(II) correlate linearly with their antimalarial activity. 相似文献