Abstract:
:A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part(.) The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Nepali K,Sharma S,Sharma M,Bedi PM,Dhar KLdoi
10.1016/j.ejmech.2014.03.018subject
Has Abstractpub_date
2014-04-22 00:00:00pages
422-87eissn
0223-5234issn
1768-3254pii
S0223-5234(14)00222-0journal_volume
77pub_type
杂志文章,评审abstract::Small molecules that can restore biological function to the p53 mutants found in human cancers have been highly sought to increase the anticancer efficacy. In efforts to generate hybrid anticancer drugs that can impact two or more targets simultaneously, we designed and developed piperlongumine (PL) derivatives with a...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.10.052
更新日期:2016-01-01 00:00:00
abstract::A series of trifluoromethyl-substituted hexahydropyrimidine derivatives were efficiently synthesized in excellent yields via one-pot three-component reaction of aromatic aldehydes, ethyl trifluoroacetoacetate and thiourea(urea) in presence of p-toluenesulfonic acid under solvent-free conditions at room temperature by ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.09.036
更新日期:2011-11-01 00:00:00
abstract::A series of (1,2,4)triazole[4,3-a]pyridine (TZP) derivatives have been designed and synthesized. Compound 8d was identified as having the most potent inhibitory activity on NO release in response to lipopolysaccharide (LPS) stimulation and inhibition of the migration induced by MCP-1 protein on RAW264.7 macrophages. B...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2019.06.025
更新日期:2019-10-01 00:00:00
abstract::To enhance the potency, reduce the side effects and improve oral property of estradiol in estrogen replacement therapy (ERT), 6 novel estradiol-RGD octapeptide conjugates have been prepared. In an ovariectomized mouse osteoporotic model, at an oral dosage of 110.3 nmol/kg per day, their anti-osteoporosis activity was ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.09.036
更新日期:2009-04-01 00:00:00
abstract::Melanoma is an aggressive form of skin cancer and it is generally associated with poor prognosis in patients with late-stage disease. Due to the increasing occurrence of melanoma, there is a need for the development of novel therapies. A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyr...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.12.001
更新日期:2016-01-27 00:00:00
abstract::Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivatives targeting the inhibition of mycolic acid biosynthesis. Among ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.09.083
更新日期:2017-01-05 00:00:00
abstract::A new series of potential GABA uptake inhibitors starting from of 1H-imidazol-4-ylacetic acid with the carboxylic acid side chain originating from different positions and varying in length have been synthesized and tested for the inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK c...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.01.042
更新日期:2011-05-01 00:00:00
abstract::Azetidin-2-ones, commonly referred as β-lactams, represent a unique ring system, with interesting chemistry and great biological potential. Besides its well known antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers. The biological and pharmacological profi...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2014.01.002
更新日期:2014-03-03 00:00:00
abstract::In continuation of our research program for new antituberculosis drugs, we have designed, synthesized and evaluated antimycobacterial activity of new series of 1-[3-(4-benzotriazol-1/2-yl-3-fluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-3-substituted-thiourea derivatives against different Mycobacterium species i.e. M. tu...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2005.12.005
更新日期:2006-03-01 00:00:00
abstract::2-(5-Arylfurfurylidene/5-nitrofurfurylidene)-5-aryl-7-(2,4-dichloro-5-fluorophenyl)-5H-thiazolo[2,3-b]-pyrimidin-2(1H)-ones 5 and 6 are synthesized by a novel three component reaction of 4,6-diarylpyrimidino-2(1H)-thiones 4, monochloroacetic acid, arylfurfuraldehydes and 5-nitro-2-furfuraldenediacetate, respectively. ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2004.06.001
更新日期:2004-09-01 00:00:00
abstract::Nine 2-arylthiazolidine-4-carboxylic acid derivatives and nine 3-tert-butoxycarbonyl-2-arylthiazolidine-4-carboxylic acid derivatives were synthesized to screen for their antibacterial activities. Compounds 5, 14-18 were first reported. Their chemical structures were clearly determined by (1)H NMR, (13)C NMR, ESI mass...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.04.014
更新日期:2009-10-01 00:00:00
abstract::In this study, some aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketones, aryl (3-methyl-benzofuran-2-yl) ketoximes and aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketoximes were synthesised starting from 2-aryloyl-3-methyl-benzofuranes. The structure elucidation of the compounds was perfo...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2005.12.013
更新日期:2006-05-01 00:00:00
abstract::A new series of pyrazolo[3,4-d]pyridazin-7-one derivatives were synthesised and evaluated for their in vitro antileishmanial activity against Leishmania amazonensis promastigote and axenic amastigote forms. The results showed that the pyrazolo[3,4-d]-pyridazin-7-one-N-acylhydrazone-(bi)thiophene hybrids 5b, 6b and 6d ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.08.048
更新日期:2016-11-29 00:00:00
abstract::Design and synthesis of a new series of 5,6-diarylimidazo[2,1-b]thiazole derivatives possessing terminal aryl sulfonamide moiety are described. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 8a, 8b, 8n, 8q, 8t, ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.03.065
更新日期:2015-05-05 00:00:00
abstract::It has been found that selective N1-alkylation of 3,4-dihydropyrimidine-2(1H)-ones can be achieved under solvent-less, mild phase transfer catalytic (PTC) conditions with tetrabutylammonium hydrogen sulfate and 50% aqueous NaOH as the catalyst and base, respectively. The procedure is tolerant to substitutional variati...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.10.002
更新日期:2009-05-01 00:00:00
abstract::Current drugs available in clinic for Alzheimer's disease (AD) treatment can only alleviate disease symptoms without clearly curing or delaying the process of AD. And some AD drugs failed in Phase III clinical trials are only focused on targeting amyloid-β (Aβ). Therefore, an alternative strategy in AD drug design is ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2020.112997
更新日期:2020-11-06 00:00:00
abstract::A series of 1,8-diazaanthraquinone derivatives carrying a 3-dialkylaminomethyl or a 3-(N-alkyl or aryl)carbamoyloxymethyl substituent was synthesised and their in vitro cytotoxic activities were evaluated against eight human cancer cell lines (HOP62, SK-OV-3, HCT-15, SF295, MCF7, SNU-354, KB-3-1 and KB-V-1). A number ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(03)00118-1
更新日期:2003-07-01 00:00:00
abstract::Eluding the involvement of solvents in organic synthesis and introducing environment friendly procedures can control environmental problems. A facile and an efficient solvent free mechanochemical method (grinding) is achieved to synthesize novel bis-biphenyl substituted thiazolidinones using non-toxic and cheap N-acet...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2017.04.021
更新日期:2017-07-07 00:00:00
abstract::A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluate...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.12.050
更新日期:2016-04-13 00:00:00
abstract::A series of heterocyclic organobismuth(III) compounds 2 [ClBi(5-R-C6H(3)-2-SO2C6H(4)-1'-): R=Me, Ph, MeO, Cl, H, t-Bu, CF3, F, Me2N] was synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antifungal activity against the yeast Saccharomyc...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.11.031
更新日期:2011-02-01 00:00:00
abstract::In the present study the synthesis of new Linezolid-like molecules has been achieved by substitution of the oxazolidinone central heterocyclic moiety with a 1,2,4-oxadiazole ring. Two series of 1,2,4-oxadiazoles, bearing different side-chains and containing a varying number of fluorine atoms, were synthesized and prel...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.02.002
更新日期:2012-04-01 00:00:00
abstract::It is a challenging task to design target-specific and less toxic non-steroidal aromatase inhibitors (NSAIs) though the modeling studies for designing anti-aromatase molecules have been continuing for more than two decades to fight the dreaded estrogen-dependent breast cancer. In this article, different validated QSAR...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2017.05.041
更新日期:2017-09-08 00:00:00
abstract::A series of (2E,4E)-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-ones (3a-r) and (2Z,4E)-3-hydroxy-1-(2-hydroxyphenyl)-5-phenylpenta-2,4-dien-1-ones (6a-l) were synthesized and evaluated in vitro as inhibitors of the two human Monoamine oxidase (hMAO) isoforms, MAO-A and MAO-B. Most of the compounds showed a selective...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.11.006
更新日期:2013-01-01 00:00:00
abstract::Δ2-Troglitazone derivatives were shown to exhibit anti-proliferative activity in a PPARγ-independent manner. We prepared various compounds in order to increase their potency and decrease their toxicity towards non-malignant primary cultured hepatocytes. Many compounds induced viabilities less than 20% at 10 μM on vari...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.015
更新日期:2014-08-18 00:00:00
abstract::The pyrrolo[1,2-f]phenanthridines 8-22 and the corresponding non-rigid analogues 23-41 were synthesised and their ability to inhibit the replication of HIV-1 was tested. Only the polycyclic derivatives 10, 11, and 13 showed a weak anti-HIV activity, whereas several pyrrolo-phenanthridines (8, 10, 16-18) were found to ...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(01)01289-2
更新日期:2002-01-01 00:00:00
abstract::A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b, 10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the reaction of phot...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.11.010
更新日期:2014-01-01 00:00:00
abstract::In this manuscript the synthesis and biological activity of novel heterocyclic derivatives of benzofuran-2-carboxamides 3a-j and 6a-f is presented. Biological evaluation in vitro revealed that only few compounds exerted concentration-depended antiproliferative effects on tumour cell lines at micromolar concentrations....
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2012.11.009
更新日期:2013-01-01 00:00:00
abstract::A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different t...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2016.01.051
更新日期:2016-03-23 00:00:00
abstract::A novel synthesis of highly substituted pyrrole-N-acetic derivatives is described through the coupling of 1,4-diketones with amino acids following Paal-Knorr's approach. These pyrrole-N-acetic acid derivatives are found to exhibit potent anti-mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tub...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2014.06.075
更新日期:2014-09-12 00:00:00
abstract::Several novel semicarbazone derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spermidine-mimetic moiety. All derivatives presented the E-configuration, as determined by NMR-NOE experiments. These compounds were tested in vitro as potential antitrypan...
journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0223-5234(00)00131-8
更新日期:2000-03-01 00:00:00