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Biomedical subjects

C Bailly

Publications and source records attributed to C Bailly.

At least 19 recordsLinked to original sources
PubMed2006

[Retained ovarian remnant carcinoma: a case report].

Ovarian remnant syndrome is defined as residual ovarian tissue non intentionally left in place by the surgeon during a bilateral salpingo-oophorectomy. Patients present various symptoms usually including chronic pelvic pain, pelvic mass, bowel obstruction, hydronephrosis due to ureteral compression. We report a case of adenocarcinoma arising in such an ovarian remnant revealed by vaginal bleeding 5 years after total abdominal hysterectomy and bilateral oophorectomy for uterine fibroids. It was regarded as stage IIIc according to the FIGO classification because of common iliac lymph node involvement while there was no ascitis, no peritoneal nor omental implant but a unilateral hydronephrosis induced by extrinsec ureteral obstruction. Complete cytoreductive surgery was achieved including partial bladder and lower ureteral resection with colpectomy, omentectomy, pelvic and para-aortic lymphadenectomy. Paclitaxel-Platinum combination chemotherapy was given for nine cycles.

Adult↗
PubMed2005

Simultaneous determination of inorganic anions and organic acids in amine solutions for sour gas treatment by capillary electrophoresis with indirect UV detection.

A new CE method has been developed for the simultaneous determination of selected inorganic anions (bromide, chloride, thiosulfate, nitrite, nitrate, sulfate, thiocyanate, fluoride and phosphate) and organic acids (oxalic, malonic, formic, tartric, acetic, glycolic, propionic, butyric and cyclohexanoic) in amine solutions from sour gas treatment units. An electrolyte composed of 10 mM trimellitic acid, 200 mM Tris (pH 9.0), 0.1% polyvinyl alcohol provides a satisfactory separation of all analytes of interest. The electroosmotic flow is reversed by using hexadimethrine bromide as a semi-permanent positively charged coating, making the electrolyte free of additive. Indirect UV detection at 240 nm is used because of the weak absorbing properties of most of analytes. The addition of 1% diethanolamine in standard mixtures permits to better preserve them, inhibiting potential degradation processes, especially for thiosulfate. The quantification is performed using internal standardization, by which molybdate is used as internal standard. Moreover, the use of relative migration times and the excellent repeatabilities obtained allow unambiguous identification of analytes in real samples by comparison with standard mixture. It has been shown that no significant matrix effect came from the presence of 30% diethanolamine in amine solution samples and the developed method was characterized in terms of calibration linearity and accuracy using recovery tests. In short, the developed method allows the simultaneous and rapid determination, in difficult matrices, of numerous inorganic anions and organic acids characterized by a large range of electrophoretic mobilities.

Anions↗
PubMed2005

Cytotoxic and antitumor potentialities of aporphinoid alkaloids.

Aporphinoids form an important group of plant secondary metabolites. Some of these compounds are used for a long time in traditional medicine for the treatment of various diseases, from benign syndromes to more severe illnesses. More than 500 aporphine alkaloids have been isolated from various plant families and many of these compounds display potent cytotoxic activities which may be exploited for the design of anticancer agents. Here we review the origin, biosynthesis, structure and cytotoxic properties of the prominent members of this class of compounds. Simple aporphinoids (boldine, dicentrine) as well as oxo-, pro- and dehydro-aporphines, and dimeric forms such as thalicarpine, are discussed here. Their mechanisms of action are not well known but DNA-manipulating enzymes such as polymerases and topoisomerases are among the most frequently cited targets for these benzylisoquinoline compounds. This review presents an updated view of the cytotoxic properties of the aporphinoids and their potential contribution to the development of anticancer agents.

Alkaloids↗
PubMed2004

Determination of diethanolamine or N-methyldiethanolamine in high ammonium concentration matrices by capillary electrophoresis with indirect UV detection: application to the analysis of refinery process waters.

Alkanolamines such as diethanolamine (DEA) and N-methyldiethanolamine (MDEA) are used in desulfurization processes in crude oil refineries. These compounds may be found in process waters following an accidental contamination. The analysis of alkanolamines in refinery process waters is very difficult due to the high ammonium concentration of the samples. This paper describes a method for the determination of DEA in high ammonium concentration refinery process waters by using capillary electrophoresis (CE) with indirect UV detection. The same method can be used for the determination of MDEA. Best results were achieved with a background electrolyte (BGE) comprising 10 mM histidine adjusted to pH 5.0 with acetic acid. The development of this electrolyte and the analytical performances are discussed. The quantification was performed by using internal standardization, by which triethanolamine (TEA) was used as internal standard. A matrix effect due to the high ammonium content has been highlighted and standard addition was therefore used. The developed method was characterized in terms of repeatability of migration times and corrected peak areas, linearity, and accuracy. Limits of detection (LODs) and quantification (LOQs) obtained were 0.2 and 0.7 ppm, respectively. The CE method was applied to the determination of DEA or MDEA in refinery process waters spiked with known amounts of analytes and it gave excellent results, since uncertainties obtained were 8 and 5%, respectively.

Electrolytes↗
PubMed2004

Phenyl substitution of furamidine markedly potentiates its anti-parasitic activity against Trypanosoma cruzi and Leishmania amazonensis.

Furamidine (DB75) and related unfused aromatic diamidines have proven useful for the treatment of parasitic infections. These compounds were primarily developed to combat infections by Pneumocystis carinii and African trypanosomes but they are also active against other parasites. Here we have investigated the in vitro effects of DB75 and its phenyl-substituted analog DB569 on two kinetoplastid haemoflagellates Trypanosomatidae: Trypanosoma cruzi and Leishmania (L) amazonensis. The phenyl-amidine compound DB569 has equivalent DNA binding properties compared to DB75 but it was selected on the basis of its distinct tumor cell distribution properties. We found that DB569 is significantly more potent than DB75 at reducing the proliferation of the parasites, using either isolated parasites in cultures or with cardiomyocyte and macrophage host cells. DB569 is effective towards the intracellular forms of T. cruzi (IC(50) in the low-micromolar range) and it exhibits trypanocidal dose-dependent effects against trypomastigote forms of T. cruzi parasites obtained from the Y strain and Dm28c clone, which belong to two different biodemes. Fluorescence microscopy experiments indicated that both diamidines were mostly localized in the nucleus of the mammalian host cells and within the nuclei and kinetoplast of the parasites. Electron microscopy studies showed that the treatment of the parasites with DB75 and DB569 induces important alterations of the parasite nucleus and kinetoplast, at sites where their DNA target is localized. Altogether, the data suggest that the phenyl-substituted furamidine analogue DB569 is a potential new candidate for the treatment of the Chagas' disease and Leishmaniasis.

Animals↗
PubMed2003

Host and parasite apoptosis following Trypanosoma cruzi infection in in vitro and in vivo models.

The mechanism of cell death which occurs during Chagas' cardiopathy is disputed. To address this issue we analyzed the molecular pathways implicated in the death of cardiomyocytes during T. cruzi invasion and found that they undergo apoptosis during both in vitro and in vivo infections. However, the death rates and onset were related to the parasite stocks belonging to different biodemes, which can be correlated to the different histological inflammation findings that have already been reported. Our in vitro data provide additional support for this hypothesis since higher levels and earlier apoptosis induction were noted during the interaction with the Dm28c (type I) as compared to the Y and CL stocks (type II). Modifications of the surface carbohydrates of the infected cardiomyocytes were observed and these molecular events may be acting as "eat me" tags for their final engulfment by macrophages and/or other non-professional phagocytes. The analysis of other host cell types showed that the in vitro infection of fibroblasts did not result in host apoptosis even when a highly infective stock was used. Conversely, infected macrophages undergo apoptosis but at a higher degree than cardiomyocytes. Apoptotic intracellular parasites were observed to varied extents depending on the T. cruzi stock, which was related to the parasite invasion and proliferation. In summary, our results show that during T. cruzi infection, the extent of apoptosis varies according to the host cell type and the parasite stocks. The apoptosis of both host and T. cruzi can contribute to the silent spreading and persistence of the parasite without triggering an exacerbated inflammatory response.

Animals↗
PubMed2003

Mechanistic and anti-proliferative studies of two novel, biologically active bis-benzimidazoles.

We have previously synthesised a number of novel head-to-head bis-benzimidazole derivatives that are structurally related to the fluorochrome, Hoechst 33258, and which possess strong affinity for A:T sites in the minor groove of duplex DNA. Initial studies revealed these compounds to exhibit potent antiproliferative activity against a range of ovarian cell lines and to inhibit transcription in an in vitro setting. In this study, we have examined their cellular behaviour in detail and have shown that two of these compounds (ABA13 and ABA833) potently inhibit the proliferation of a range of human tumour cell lines, and show some specificity towards breast carcinoma cell lines. In most of the cell lines investigated, ABA833 was the more potent of the two compounds. Flow cytometric analysis revealed that ABA13 and ABA833 (50-500 nM) induced an S phase block and increased the pre-G1 population in MCF-7 and MDA 468 human breast cancer cells. An increase in the pre-G1 population of RKO colon carcinoma cells was seen only at 500 nM with ABA833, reflecting the reduced sensitivity of this cell line to the bis-benzimidazoles in comparison to the breast cancer cell lines. Mechanistic studies revealed that neither ABA13 or ABA833 act as topoisomerase I (topo I) or topoisomerase II (topo II) poisons in plasmid or kinetoplast DNA (kDNA) relaxation assays, but both compounds do inhibit the catalytic activity of these enzymes. Drug uptake studies showed that reduced sensitivity of MCF-7adr and RKO cells compared with MCF-7 to both ABA13 and ABA833 correlated with a markedly reduced intracellular drug accumulation.

Antineoplastic Agents↗
PubMed2003

High-dose BCNU followed by autologous hematopoietic stem cell transplantation in supratentorial high-grade malignant gliomas: a retrospective analysis of 114 patients.

Conventional treatment of high-grade glioma includes maximal surgical resection followed by external radiation therapy. Despite this treatment, the prognosis for patients is poor. High doses of chemotherapy might be another way to increase the response rate and median survival. Increasing doses of BCNU might be more effective, but also provokes unacceptable myelotoxicity. This dose-limiting toxicity can be circumvented by using autologous blood stem cell rescue. We report our experience of high-dose BCNU followed by transplantation of autologous hematopoietic stem cells in 114 patients with high-grade gliomas. Of the 114 gliomas, 78 were glioblastoma multiforme (GM) (68%), 24 anaplastic astrocytomas (AA) (21%), and 12 anaplastic oligodendrogliomas (OD) (11%). Complete surgical resection was performed for 22 patients (18 GM and 4 AA). The median age was 44 years (range 17-65). A total of 84 patients received autologous hematopoietic stem cells from bone marrow harvest, while 30 patients received granulocyte colony-stimulating factor followed by apheresis and received peripheral blood progenitor cells (PBPC). High dose of BCNU (800 mg/m(2)) was given at least 1 month after neurosurgery. Bone marrow or PBPC was transplanted 48-72 h after chemotherapy. Radiotherapy was started approximately 40 days after transplantation to a total of 60 Gy. Median follow-up was 89 months (19-163). The overall survival (OS) was, respectively, 12 months for GM, 37 months for OD and 81 months for AA. Histological type appeared to be the main discriminating factor, with a worse prognosis for GM. Within the GM population, age, completeness of surgery, and response appeared to be one important prognostic factors. The AA and OD populations were small to reliably assess prognostic factors. On multivariate analysis, the main prognostic factors were histologic type, quality of surgery, and age (P<0.005). Five of 114 patients had lethal complications from the procedure. Four of these patients had a Karnovsky performance score (KPS) of 60%. The protocol thus appears to be feasible but patients should be selected for KPS more than 70%. We observed long-term survivors, although the OS and the time to treatment failure seem to be comparable to that described for other treatment. Additional pilot studies are unlikely to reveal more than a modest benefit from this procedure and therefore a randomized study should be performed.

Adolescent↗
PubMed2003

Relevance of vertical growth pattern in thin level II cutaneous superficial spreading melanomas.

Thin (<or=0.76 mm) level II cutaneous superficial spreading melanomas (SSMs) are known to be of excellent prognosis and very few recur, metastasize, or are lethal. Although many prognostic features at this stage have been studied, none appears to be statistically significant. The concept of tumor growth phase is correlated with Clark's level except for level II. SSM level II show either an invasive vertical growth phase or an invasive radial growth phase. The aim of our study (retrospective, multicenter, and case-control type) was to investigate the prognostic impact of vertical growth phase in thin level II cutaneous SSM. We identified 12 patients of poor outcome with complete initial excision. Each case was matched with three controls for gender, age, location, tumor thickness, and follow-up period since diagnosis. Independent pathologists studied all cases and controls. Univariate analyses were performed with a conditional logistic regression method. A kappa test was used to assess reproducibility between pathologists. Our study is the first and largest that shows that vertical growth phase is the only statistically significant prognostic factor for thin level II cutaneous SSM. We propose that growth phase evaluation (a minimum of eight serial sections being mandatory not to underdiagnose vertical growth phase) should be added to the recommendations for melanoma histologic report, at least for level II SSM.

Adult↗
PubMed2002

Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients.

Allogeneic hematopoietic stem cell transplantation is often used to treat hematologic malignancies. The efficacy of this procedure is due to both myeloablative conditioning and graft-versus-leukemia (GVL). However, the disadvantages of allogeneic transplantation include graft-versus-host disease (GVHD), relapse from the original tumor, and patient susceptibility to opportunistic infections. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft-versus-tumor (GVT), like GVL, will have a significant anti-tumor effect. This effect has been demonstrated in renal carcinomas, and with less evidence in breast cancers. Five patients with malignant ovarian tumors resistant to chemotherapy underwent allogeneic transplantation, four from bone marrow, and one from peripheral blood stem cells. All donors were HLA-identical siblings. One patient received a myeloablative conditioning regimen, while the other four received a non-myeloablative regimen. Two patients received donor lymphocyte infusions (DLI). Four of the patients presented with acute or chronic GVHD associated with tumor regression of at least 50%. These tumor regressions were measured by CA-125 levels and CT scans. The fifth patient died of rapid progression just after transplantation. Of the four transplantation survivors, three received a non-myeloablative regimen which did not seem to reduce treatment effectiveness. While it did reduce toxicity, one of these patients died of GVHD after 127 days. DLI was administered to two patients. These infusions seemed to promote GVHD which was able to control disease progression for one patient and had no apparent effect on the other. Allograft of hematopoietic stem cells might be of interest in ovarian cancer. The results in one patient also suggest that DLI may be an effective immunotherapy, although doses and timing need to be determined. The number of cases presented is small, however, and clinical experience on a larger scale will be required to determine the real clinical efficacy of graft versus cancerous ovarian cells.

Adult↗
PubMed2001

DNA interaction and cytotoxicity of a new series of indolo[2,3-b]quinoxaline and pyridopyrazino[2,3-b]indole derivatives.

Absorption, melting temperature and linear dichroism measurements were performed to investigate the interaction with DNA of a series of 16 tricyclic and tetracyclic compounds related to the antiviral agent B-220. The relative DNA affinity of the test compounds containing an indolo[2,3-b]quinoxaline, pyridopyrazino[2,3-b]indoles or pyrazino[2,3-b]indole planar chromophore varies significantly depending on the nature of the side chain grafted onto the indole nitrogen. Compounds with a dimethylaminoethyl chain strongly bind to DNA and exhibit a preference for GC-rich DNA sequences, as revealed by DNase I footprinting. Weaker DNA interactions were detected with those bearing a morpholinoethyl side chain. The incorporation of a 2,3-dihydroxypropyl side chain does not reinforce the DNA interaction compared with the unsubstituted analogues. Both the DNA relaxation assay and cytotoxicity study using two human leukemia cell lines sensitive (HL-60) or resistant (HL-60/MX2) to the antitumor drug mitoxantrone, indicate that topoisomerase II is not a privileged target for the test compounds which only weakly interfere with the catalytic activity of the DNA cleaving enzyme. Cytometry studies showed that the most cytotoxic compounds induce a massive accumulation of cells in the G2/M phase of the cell cycle. Collectively, the data show a relationship between DNA binding and cytotoxicity in the indolo[2,3-b]quinoxaline series.

Animals↗
PubMed2001

Specific inhibition of serine- and arginine-rich splicing factors phosphorylation, spliceosome assembly, and splicing by the antitumor drug NB-506.

Specific phosphorylation of serine- and arginine-rich pre-mRNA splicing factors (SR proteins) is one of the key determinants regulating splicing events. Several kinases involved in SR protein phosphorylation have been identified and characterized, among which human DNA topoisomerase I is known to have DNA-relaxing activity. In this study, we have investigated the mechanism of splicing inhibition by a glycosylated indolocarbazole derivative (NB-506), a potent inhibitor of both kinase and relaxing activities of topoisomerase I. NB-506 completely inhibits the capacity of topoisomerase I to phosphorylate, in vitro, the human splicing factor 2/alternative splicing factor (SF2/ASF). This inhibition is specific, because NB-506 does not demonstrate activity against other kinases known to phosphorylate SF2/ASF such as SR protein kinase 1 and cdc2 kinase. Importantly, HeLa nuclear extracts competent in splicing but not splicing-deficient cytoplasmic S100 extracts treated with the drug fail to phosphorylate SF2/ASF and to support splicing of pre-mRNA substrates containing SF2/ASF-target sequences. Native gel analysis of splicing complexes revealed that the drug affects the formation of the spliceosome, a dynamic ribonucleoprotein structure where splicing takes place. In the presence of the drug, neither pre-spliceosome nor spliceosome is formed, demonstrating that splicing inhibition occurs at early steps of spliceosome assembly. Splicing inhibition can be relieved by adding phosphorylated SF2/ASF, showing that extracts treated with NB-506 lack a phosphorylating activity required for splicing. Moreover, NB-506 has a cytotoxic effect on murine P388 leukemia cells but not on P388CPT5 camptothecin-resistant cells that carry two point mutations in conserved regions of topoisomerase I gene (Gly361Val and Asp709Tyr). After drug treatment, P388 cells accumulated hypophosphorylated forms of SR proteins and polyadenylated RNA in the nucleus. In contrast, neither SR protein phosphorylation nor polyadenylated mRNA distribution was affected in P388 CPT5-treated cells. Consistently, NB506 treatment altered the mRNA levels and/or splicing pattern of several tested genes (Bcl-X, CD 44, SC35, and Sty) in P388 cells but not in P388 CPT5 cells. The study shows for the first time that indolocarbazole drugs targeting topoisomerase I can affect gene expression by modulating pre-mRNA splicing through inhibition of SR proteins phosphorylation.

Animals↗
PubMed2001

Recognition of ATGA sequences by the unfused aromatic dication DB293 forming stacked dimers in the DNA minor groove.

Furamidine and related diamidines represent a promising series of drugs active against widespread parasites, in particular the Pneumocystic carinii pathogen. In this series, the phenylfuranbenzimidazole diamidine derivative DB293 was recently identified as the first unfused aromatic dication capable of forming stacked dimers in the DNA minor groove of GC-containing sequences. Here we present a detailed biochemical and biophysical characterization of the DNA sequence recognition properties of DB293. Three complementary footprinting techniques using DNase I, Fe(II)-EDTA, and an anthraquinone photonuclease were employed to locate binding sites for DB293 in different DNA restriction fragments. Two categories of sites were identified by DNase I footprinting: (i) 4/5 bp sequences containing contiguous A.T pairs, such as 5'-AAAA and 5'-ATTA; and (ii) sequences including the motif 5'-ATGA.5'-TCAT. In particular, a 13-bp sequence including two contiguous ATGA motifs provided a highly preferential recognition site for DB293. Quantitative footprinting analysis revealed better occupancy of the 5'-ATGA site compared to the AT-rich sites. Preferential binding of DB293 to ATGA sites was also observed with other DNA fragments and was confirmed independently by means of hydroxyl radical footprinting generated by the Fe(II)-EDTA system, as well as by a photofootprinting approach using the probe anthraquinone-2-sulfonate (AQS). In addition, this photosensitive reagent revealed the presence of sites of enhanced cutting specific to DB293. This molecule, but not other minor groove binders such as netropsin, induces specific local structural changes in DNA near certain binding sites, as independently shown by DNase I and the AQS probe. Recognition of the ATGA sequence by DB293 was investigated further using melting temperature experiments and surface plasmon resonance (SPR). The use of different hairpin oligonucleotides showed that DB293 can interact with AT sites via the formation of 1:1 drug-DNA complexes but binds much more strongly, and cooperatively, to ATGA-containing sequences to form 2:1 drug-DNA complexes. DB293 binds strongly to ATGA sequences with no significant context dependence but is highly sensitive to the orientation of the target sequence. The formation of 2:1 DB293/DNA complexes is abolished by reversing the sequence 5'-ATGA-->3'-ATGA, indicating that directionality plays an important role in the drug-DNA recognition process. Similarly, a single mutation in the A[T-->G]GA sequence is very detrimental to the dimer interactions of DB293. From the complementary footprinting and SPR data, the 5'-ATGA sequence is identified as being a highly favored dimer binding site for DB293. The data provide clues for delineating a recognition code for diamidine-type minor groove binding agents, and ultimately to guide the rational design of gene regulatory molecules targeted to specific sites of the genetic material.

Antifungal Agents↗
PubMed2001

Novel dications with unfused aromatic systems: trithiophene and trifuran derivatives of furimidazoline.

We report the synthesis, interaction with DNA, topoisomerase II inhibition, and cytotoxicity of two novel unfused aromatic dications derived from the antimicrobial agent furimidazoline. The central diphenylfuran core of furimidazoline has been replaced with a trithiophene (DB358) or a trifuran (DB669) unit and the terminal imidazoline groups were preserved. The strength and mode of binding of the drugs to nucleic acids were investigated by complementary spectroscopic techniques including spectrophotometric, surface plasmon resonance, circular and linear dichroism measurements. The trifuran derivative forms intercalation complexes with double-stranded DNA, whereas the mode of binding of the trithiophene derivative varies depending on the drug/DNA ratio, as independently confirmed by NMR spectroscopic studies performed with (A-T)7 and (G-C)7 oligomers. Two-dimensional NMR data provided a molecular model for the binding of DB358 within the minor groove of the AATT sequence of the decanucleotide d(GCGAATTCGC)(2). DNase I footprinting experiments confirmed the sequence-dependent binding of DB358 to DNA. The trithiophene derivative interacts preferentially with AT-rich sequences at low concentrations, but can accomodate GC sites at higher concentrations. DNA relaxation assays revealed that DB358 stimulated DNA cleavage by topoisomerase II, in contrast to DB669. The substitution of N-alkylamidines for the imidazoline terminal groups abolished the capacity of the drug to poison topoisomerase II. At the cellular level, flow cytometry analysis indicated that DB358, which is about six times more cytotoxic than the trifuran analogue, induced a significant accumulation of HL-60 human leukemia cells in the G2/M phase. The incorporation of thiophene heterocycles appears as a convenient procedure to limit the strict AT selectivity of dications containing an extended unfused aromatic system and to design cytotoxic DNA intercalating agents acting as poisons for human topoisomerase II.

Anti-HIV Agents↗
PubMed2001

DNA interaction of the tyrosine protein kinase inhibitor PD153035 and its N-methyl analogue.

The brominated anilinoquinazoline derivative PD153035 exhibits a very high affinity and selectivity for the epidermal growth factor receptor tyrosine kinase (EGF-R TK) and shows a remarkable cytotoxicity against several types of tumor cell lines. In contrast, its N-methyl derivative, designated EBE-A22, has no effect on EGF-R TK but maintains a high cytotoxic profile. The present study was performed to explore the possibility that PD153035 and its N-methyl analogue might interact with double-stranded DNA, which is a primary target for many conventional antitumor agents. We studied the strength and mode of binding to DNA of PD153035 and EBE-A22 by means of absorption, fluorescence, and circular and linear dichroism as well as by a relaxation assay using human DNA topoisomerases. The results of various optical and gel electrophoresis techniques converge to show that both drugs bind to DNA and behave as typical intercalating agents. In particular, EBE-A22 unwinds supercoiled plasmid, stabilizes duplex DNA against heat denaturation, and produces negative CD and ELD signals, as expected for an intercalating agent. Extensive DNase I footprinting experiments performed with a large range of DNA substrates show that EBE-A22, but not PD153035, interacts preferentially with GC-rich sequences and discriminates against homooligomeric runs of A and T which are often cut more readily by the enzyme in the presence of the drug compared to the control. Altogether, the results provide the first experimental evidence that DNA is a target of anilinoquinazoline derivatives and suggest that this N-methylated ring system is a valid candidate for the development of DNA-targeted cytotoxic compounds. The possible relevance of selective DNA binding to activity is considered. The unexpected GC-selective binding properties of EBE-A22 entreat further exploration into the use of N-methylanilinoquinazoline derivatives as tools for designing sequence-specific DNA binding ligands.

Antineoplastic Agents↗