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1.
Biomacromolecules ; 22(9): 3926-3940, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34383466

RESUMO

Photodynamic/photothermal therapy (PDT/PTT) that deploys a near-infrared responsive nanosystem is emerging to be a promising modality in cancer treatment. It is highly desirable to have a multifunctional nanosystem that can be used for efficient tumor targeting and inhibiting metastasis/recurrence of cancer. In the current study, self-assembled chlorophyll-rich fluorosomes derived from Spinacia oleracea were developed. These fluorosomes were co-assembled on a polydopamine core, forming camouflaged nanoparticles (SPoD NPs). The SPoD NPs exhibited a commingled PDT/PTT (i.e., interdependent PTT and PDT) that inhibited both normoxic and hypoxic cancer cell growth. These nanoparticles showed stealth properties with enhanced physiological stability and passive tumor targeting. SPoD NPs also exhibited tumor suppression by synergistic PTT and PDT. It also prevented lung metastasis and splenomegaly in tumor-bearing Balb/c mice. Interestingly, treatment with SPoD NPs also caused the suppression of secondary tumors by eliciting an anti-tumor immune response. In conclusion, a co-assembled multifunctional nanosystem derived from S. oleracea showed enhanced stability and tumor-targeting efficacy, resulting in a commingled PDT/PTT effect.


Assuntos
Nanopartículas , Fotoquimioterapia , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Humanos , Indóis , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Terapia Fototérmica , Polímeros , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
2.
Arch Pharm (Weinheim) ; 350(3-4)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28326602

RESUMO

Acetylcholinesterase (AChE) inhibitors are currently the most widely prescribed drugs for Alzheimer's disease. The high potential of indole compounds in medicinal chemistry led us to discover a novel series of fluoroindole compounds. The synthesis and pharmacological analysis of the difluoropyrido[4,3-b]indoles 11-34 are described. Compounds 11-34 were tested for AChE inhibition activity using a rat brain homogenate. Compounds 25-29 display a promising in vitro profile with an IC50 value range of 46-51.6 nM and show significant protective effect on scopolamine-induced amnesia. The present data indicate that compounds 25-29 may represent attractive potent molecules for the treatment of Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Amnésia/tratamento farmacológico , Carbolinas/farmacologia , Inibidores da Colinesterase/farmacologia , Animais , Células CHO , Carbolinas/síntese química , Carbolinas/química , Células Cultivadas , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Cricetulus , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
3.
Arch Pharm (Weinheim) ; 349(7): 566-71, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27231098

RESUMO

A series of new N-(substituted)-1-methyl-2,4-dioxo-1,2-dihydroquinazoline-3(4H)-carboxamides were designed, synthesized, and evaluated for their anticonvulsant activity. Most of the synthesized compounds exhibited potent anticonvulsant activities in the maximal electroshock (MES) and pentylenetetrazol (PTZ) test. The most promising compound 4c showed significant anticonvulsant activity with a protective index value of 3.58. The compounds 4a-c were also found to have encouraging anticonvulsant activity in the MES and PTZ screen when compared with the standard drugs, valproate and methaqualone. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drugs.


Assuntos
Anticonvulsivantes/síntese química , Anticonvulsivantes/uso terapêutico , Quinazolinas/síntese química , Quinazolinas/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Eletrochoque , Metaqualona/uso terapêutico , Camundongos , Pentilenotetrazol , Picrotoxina/uso terapêutico , Convulsões/induzido quimicamente , Relação Estrutura-Atividade , Ácido Valproico/uso terapêutico
4.
Arch Pharm (Weinheim) ; 347(4): 256-67, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24395602

RESUMO

A series of new 2-methyl-2-[3-(5-piperazin-1-yl-[1,3,4]oxadiazol-2-yl)-phenyl]-propionitrile derivatives 8a-o, 9a-c, 10a-d, and 11a-d were synthesized to meet the structural requirements essential for anticonvulsant property. The structures of all the synthesized compounds were confirmed by means of (1)H NMR, (13)C NMR, and mass spectral studies. The purity of the novel compounds was confirmed by elemental analyses. All the compounds were screened for their anticonvulsant activity against maximal electroshock (MES) seizure method and their neurotoxic effects were determined by rotorod test. Compounds 8d, 8e, and 8f were found to be the most potent of this series. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg). The efforts were also made to establish the structure-activity relationships among the synthesized compounds. The pharmacophore model was used to validate the anticonvulsant activity of the synthesized molecules.


Assuntos
Anticonvulsivantes/farmacologia , Nitrilas/farmacologia , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/síntese química , Anticonvulsivantes/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrochoque , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Nitrilas/síntese química , Nitrilas/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade
5.
Arch Pharm (Weinheim) ; 347(5): 370-80, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24446334

RESUMO

A series of novel 1'-[2-(difluoromethoxy)benzyl]-2'H,5'H-spiro[8-azabicyclo[3.2.1]octane-3,4'-imidazolidine]-2',5'-dione substituted hydantoins (5-32) were synthesized using an appropriate synthetic route and characterized by elemental analysis and spectral data. The novel molecules were screened for anticonvulsant activity in mice by maximal electroshock (MES) and subcutaneous pentylenetetrazol (ScPTZ)-induced seizure tests. The neurotoxicity was assessed using the rotarod method. Compounds 9, 10, 18, 30, and 31 exhibited anticonvulsant potency against MES seizure and in the ScPTZ model, with lesser neurotoxicity. Some title compounds showed lesser central nervous system depression compared to phenytoin.


Assuntos
Anticonvulsivantes/síntese química , Compostos Azabicíclicos/síntese química , Imidazolidinas/síntese química , Compostos de Espiro/síntese química , Animais , Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/toxicidade , Compostos Azabicíclicos/química , Compostos Azabicíclicos/uso terapêutico , Compostos Azabicíclicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Imidazolidinas/química , Imidazolidinas/uso terapêutico , Imidazolidinas/toxicidade , Masculino , Camundongos , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Teste de Desempenho do Rota-Rod , Convulsões/tratamento farmacológico , Compostos de Espiro/química , Compostos de Espiro/uso terapêutico , Compostos de Espiro/toxicidade
6.
Nanotheranostics ; 8(2): 239-246, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444742

RESUMO

Cancer metastasis plays a major role in failure of therapeutic avenues against cancer. Owing to metastasis, nearly 70-80% of stage IV breast cancer patients lose their lives. Nanodrug delivery systems are playing a critical role in the therapy of metastatic cancer in the recent times. This paper reports the enhanced permeation and retention (EPR) based targeting of metastatic breast cancer using a novel nano lipo-polymeric system (PIR-Au NPs). The PIR-Au NPs demonstrated an increase in fluorescence by virtue of surface coating with gold, owing to the metal enhanced fluorescence phenomenon as reported in our earlier reports. Enhanced fluorescence of PIR-Au NPs was observed in murine mammary carcinoma cell line (4T1), as compared to free IR780 or IR780 loaded nanosystems (P-IR NPs), when incubated for same time at same concentrations, indicating its potential application for imaging and an enhanced bioavailability of IR780. Significant cell death was noted with photothermal mediated cytotoxicity in-vitro against breast cancer cells (MCF-7 and 4T1). An enhanced fluorescence was observed in the zebra fish embryos incubated with PIR-Au NPs. The enhanced permeation and retention (EPR) effect was seen with PIR-Au NPs in-vivo. A strong fluorescent signal was recorded in mice injected with PIR-Au NPs. The tumor tissue collected after 72 h, clearly showed a greater fluorescence as compared to other groups, indicating the plasmon enhanced fluorescence. We also demonstrated the EPR-based targeting of the PIR-Au NPs in-vivo by means of photothermal heat. This lipo-polymeric hybrid nanosystem could therefore be successfully applied for image-guided, passive-targeting to achieve maximum therapeutic benefits.


Assuntos
Neoplasias da Mama , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Fluorescência , Ouro , Morte Celular , Temperatura Alta , Polímeros
7.
ACS Infect Dis ; 10(8): 2978-2990, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-38990322

RESUMO

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.


Assuntos
Antibacterianos , Anti-Inflamatórios , Fotoquimioterapia , Cicatrização , Peixe-Zebra , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Cicatrização/efeitos dos fármacos , Ratos , Infecção dos Ferimentos/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Infecções Estafilocócicas/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Humanos , Complicações do Diabetes/tratamento farmacológico , Masculino
8.
Arch Pharm (Weinheim) ; 346(3): 200-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23335463

RESUMO

New 3-[(2,4-dioxo-1,3,8-triazaspiro[4.6]undec-3-yl)methyl]benzonitrile derivatives 8-37 were synthesized and their pharmacological activities were determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. All the compounds were evaluated for their possible anticonvulsant activity by maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) test. Compounds 11, 18, 31, and 32 showed significant and protective effect on seizure, when compared with the standard drug valproate. The same compounds were found to exhibit advanced anticonvulsant activity as well as lower neurotoxicity than the reference drug. From this study, it is quite apparent that there are at least three parameters for the activity of anticonvulsant drugs, that is, a lipophilic domain, a hydrophobic center, and a two-electron donor.


Assuntos
Anticonvulsivantes/síntese química , Desenho de Fármacos , Nitrilas/síntese química , Compostos de Espiro/síntese química , Animais , Anticonvulsivantes/química , Anticonvulsivantes/farmacologia , Anticonvulsivantes/toxicidade , Relação Dose-Resposta a Droga , Eletrochoque , Dose Letal Mediana , Camundongos , Estrutura Molecular , Síndromes Neurotóxicas/etiologia , Nitrilas/química , Nitrilas/farmacologia , Nitrilas/toxicidade , Convulsões/tratamento farmacológico , Compostos de Espiro/química , Compostos de Espiro/farmacologia , Compostos de Espiro/toxicidade , Relação Estrutura-Atividade
9.
Biology (Basel) ; 11(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35053076

RESUMO

Autism spectrum disorder (ASD) is characterised by problems with social interaction, verbal and nonverbal communication and repetitive behaviour. In mice, the 14th postnatal day is believed to correspond to the third trimester of human embryonic development and is considered a vital period for central nervous system development. It has been shown that ASD affects 2 to 3 times more male than female individuals. In the present study, ASD was induced in 14 postnatal day (PND) BALB/c mice using valproic acid (VPA). VPA administration brought about substantial differences in the histoarchitecture of the brain in both male and female mice, linked to behavioural deficits. We observed that both male and female mice showed similar morphological changes in the prefrontal cortex, hippocampus and Purkinje cells. We also observed hair loss from PND 17 to 25, which was again similar between male and female mice. However, there were higher rates of change in the cerebral cortex, frontal cortex and temporal lobe and hippocampus in VPA-treated male animals. With respect to the cerebellum, we did not observe any alterations by haematoxylin and eosin (H&E) staining, but detailed morphological observation using scanning electron microscopy (SEM) showed a higher rate of phenotype changes in VPA-treated male animals. Moreover, 5-HT2A receptor protein levels were upregulated in the cerebral cortex, hippocampus and Purkinje cells in VPA-treated male mice compared with control animals and VPA-treated female mice, as shown by immunohistochemical analysis. Based on all these findings, we conclude that male animals are more susceptible to VPA-induced ASD than females.

10.
ACS Appl Mater Interfaces ; 13(47): 55862-55878, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34788534

RESUMO

Metastasis is one of the predisposing factors for cancer-related mortalities worldwide. Patients with advanced cancers (stage IV) receive palliative care with minimal possibility of achieving complete remission. Antibody-based therapeutic modalities are capable of targeting tumors that are confined to a particular location but are ineffective in targeting distant secondary tumors. In the current study, we have developed a smart nano-transforming hydrogel (NTG) that transforms in situ to polymeric nanoparticles (PA NPs) of 100-150 nm when injected subcutaneously. These nanoparticles targeted the primary and secondary metastatic tumors for up to ∼5 and ∼3 days, respectively. The in situ-formed PA NPs also demonstrated a pH-responsive drug release resulting in about ∼80% release within 100 h at 5.8 pH. When tested in vivo, substantial inhibition of lung metastases was observed compared to chemotherapy, thus demonstrating the efficiency of nanotransforming hydrogels in targeting and inhibiting primary and secondary metastatic tumors.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Materiais Biocompatíveis/química , Doxorrubicina/farmacologia , Hidrogéis/química , Neoplasias Pulmonares/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Nanopartículas/química , Terapia Fototérmica , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Materiais Biocompatíveis/administração & dosagem , Linhagem Celular , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Feminino , Ouro/administração & dosagem , Ouro/química , Hidrogéis/administração & dosagem , Injeções Subcutâneas , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Melanoma Experimental/patologia , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Propriedades de Superfície
11.
ACS Comb Sci ; 22(10): 509-518, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806898

RESUMO

A MoS2-supported-calix[4]arene (MoS2-CA4) nanocatalyst was used for efficient synthesis of 2,4,5-trisubstituted imidazole derivatives from 1-(4-nitrophenyl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione, aldehydes and ammonium acetate under solvent-free conditions. Reusability of the catalyst up to five cycles without any significant loss in the yields of the product is the unique feature of this heterogeneous solid catalysis. Furthermore, the noteworthy highlights of this method are safe reaction profiles, broad substrate scope, excellent yields, economical, solvent-free, and simple workup conditions. All synthesized compounds were evaluated for their in vitro antitubercular (TB) activity against Mycobacterium tuberculosis (Mtb) H37Rv. Among the screened compounds 3c, 3d, 3f, 3m, and 3r had MIC values of 2.15, 2.78, 5.75, 1.36, and 0.75 µM, respectively, and exhibited more potency than the reference drugs pyrazinamide (MIC: 3.12 µM), ciprofloxacin (MIC: 4.73 µM), and ethambutol (7.61 µM). Besides, potent compounds (3c, 3d, 3f, 3m, and 3r) have been tested for inhibition of MabA (ß-ketoacyl-ACP reductase) enzyme and cytotoxic activity against mammalian Vero cell line. A molecular docking study was carried out on the MabA (PDB ID: 1UZN) enzyme to predict the interactions of the synthesized compounds. The results of the in vitro anti-TB activity and docking study showed that synthesized compounds have a strong anti-TB activity and can be adapted and produced more effectively as a lead compound.


Assuntos
3-Oxoacil-(Proteína Carreadora de Acil) Redutase/antagonistas & inibidores , Antituberculosos/síntese química , Proteínas de Bactérias/antagonistas & inibidores , Calixarenos/química , Dissulfetos/química , Inibidores Enzimáticos/síntese química , Imidazóis/síntese química , Molibdênio/química , Mycobacterium tuberculosis/efeitos dos fármacos , Fenóis/química , Animais , Antituberculosos/farmacologia , Catálise , Chlorocebus aethiops , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacologia , Humanos , Imidazóis/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ligação Proteica , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade , Células Vero/efeitos dos fármacos
12.
Cent Nerv Syst Agents Med Chem ; 17(3): 201-208, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28707581

RESUMO

BACKGROUND: Epilepsy, one of the most frequent neurological afflictions in man characterized by excessive temporary neuronal discharges resulting in uncontrolled convulsion, requires special medical attention. Though several new anticonvulsants are introduced, some types of seizures are still not adequately treated with current therapy. Toxicity, intolerance, and lack of efficacy for certain types of seizure are some of the limitations of the current medications. METHODS: Maximal electroshock (MES) seizure model was used in the present study to evaluate the anticonvulsant activity of the drugs. Seizures were induced in ten weeks old male Wistar rats (200-220 g) by delivering electro shock of 150 mA for 0.2 sec by means of a convulsiometer through a pair of ear clip electrodes. The test compounds (1-10, 100 mg/kg) were administered by oral route 30 mins before the maximal electroshock seizure test by suspending in carboxymethylcellulose (1%). The animals were observed closely for 2 mins. The percentage of inhibition of seizure relative to control was recorded and calculated. Phenytoin (100 mg/kg, p.o) was used as a standard drug. The data was analysed by using one way ANOVA followed by dunnett's test. RESULTS: In our present series of compounds the active compounds possess all the requirements essential for anticonvulsant activity as proposed by Dimmock and others. In this study, it reveals that, compounds showing anticonvulsant activity with more lipophilic N-substitution group are more active than hydrophobic substitution in the hydantoin ring. The rapid onset of action is believed to be due to the substitution of more lipophilic propyl group in the N-substitution in the hydantoin moiety. Evidently, this distal hydrophobic centre alters the bioavailability of the molecules. CONCLUSION: The results are encouraging and show that, the hydantoins are more potential molecules for the treatment of anticonvulsant. Anticonvulsants have greatly improved the lives of people with epilepsy. Approximately 70% of patients can achieve complete freedom from seizures with appropriate treatment. Lipophilicity appears to govern the MES activity. If there is lipophilic moiety, then MES activity is favoured. All the compounds have shown promising and significant protective effect on maximal electroshock induced seizures when compared to vehicle treated control rats.


Assuntos
Anticonvulsivantes/síntese química , Anticonvulsivantes/uso terapêutico , Hidantoínas/síntese química , Hidantoínas/uso terapêutico , Convulsões/tratamento farmacológico , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Eletrochoque/efeitos adversos , Masculino , Ratos , Ratos Wistar , Convulsões/etiologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-26028406

RESUMO

A series of piperamides (PA) 8a-j were designed, synthesized and evaluated for their antimicrobial and anticonvulsant activity. Compounds 8a and 8h showed considerable antibacterial activity against B. subtilis with minimum inhibitory concentration (MIC) of 8 and 10 µg/mL, respectively. Compounds 8a and 8h showed advanced anticonvulsant activity as well as lower neurotoxicity than the reference drugs. The interaction between bovine serum albumin (BSA) and PA was investigated using fluorescence quenching and UV-vis absorption spectroscopy. Results showed that PA could strongly quinch the intrensic fluorescence of BSA through a static quencing procedure. The binding constant and number of binding sites of PA with BSA were obtained. The binding distance was calculated based on Forster non-radiative energy transfer theory.


Assuntos
Amidas/síntese química , Amidas/farmacologia , Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Piperidinas/síntese química , Piperidinas/farmacologia , Soroalbumina Bovina/metabolismo , Amidas/metabolismo , Animais , Anticonvulsivantes/metabolismo , Bactérias/efeitos dos fármacos , Sítios de Ligação , Bovinos , Transferência de Energia , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Piperidinas/metabolismo , Ligação Proteica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta
14.
Arch Pharm Res ; 35(1): 51-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22297742

RESUMO

A series of new 2-methyl-3-(2-piperazin-1-yl-ethyl)-pyrido[1,2-a]pyrimidin-4-one derivatives 6a-j were synthesized by a nucleophilic substitution reaction of 2-methyl-3-(2-piperazin-1-ylethyl)-pyrido[1,2-a]pyrimidin-4-one with various sulfonyl chlorides. The compounds were characterized by different spectral studies. All the compounds were evaluated for their antiproliferative effect using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method against four human cancer cell lines (K562, Colo-205, MDA-MB 231, IMR-32) for the time period of 24 h. Among the series, compounds 6d, 6e and 6i showed good activity on all cell lines except K562, whereas the other compounds in the series exhibited moderate activity. Compound 6d could be a potential anticancer agent and therefore deserves further research.


Assuntos
Proliferação de Células/efeitos dos fármacos , Piperazinas/síntese química , Piperazinas/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Células K562
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