CCL

Összesen 13 találat.
#/oldal:
Részletezés:
Rendezés:

1.

001-es BibID:BIBFORM049347
Első szerző:Cai, Ren-Zhi
Cím:Synthesis of new potent agonistic analogs of growth hormone-releasing hormone (GHRH) and evaluation of their endocrine and cardiac activities / Renzhi Cai, Andrew V. Schally, Tengjiao Cui, Luca Szalontay, Gabor Halmos, Wei Sha, Magdolna Kovacs, Miklos Jaszberenyi, Jinlin He, Ferenc G. Rick, Petra Popovics, Rosemeire Kanashiro-Takeuchi, Joshua M. Hare, Norman L. Block, Marta Zarandi
Dátum:2013
ISSN:0196-9781
Megjegyzések:AbstractIn view of the recent findings of stimulatory effects of GHRH analogs, JI-34, JI-36 and JI-38, on cardiomyocytes, pancreatic islets and wound healing, three series of new analogs of GHRH(1-29) have been synthesized and evaluated biologically in an endeavor to produce more potent compounds. "Agmatine analogs", MR-356 (N-Me-Tyr1-JI-38), MR-361(N-Me-Tyr1, D-Ala2-JI-38) and MR-367(N-Me-Tyr1, D-Ala2, Asn8-JI-38), in which Dat in JI-38 is replaced by N-Me-Tyr1, showed improved relative potencies on GH release upon subcutaneous administration in vivo and binding in vitro. Modification with N-Me-Tyr1 and Arg29-NHCH3 as in MR-403 (N-Me-Tyr1, D-Ala2, Arg29-NHCH3-JI-38), MR-406 (N-Me-Tyr1, Arg29-NHCH3-JI-38) and MR-409 (N-Me-Tyr1, D-Ala2, Asn8, Arg29-NHCH3-JI-38), and MR-410 (N-Me-Tyr1, D-Ala2, Thr8, Arg29-NHCH3-JI-38) resulted in dramatically increased endocrine activities. These appear to be the most potent GHRH agonistic analogs so far developed. Analogs with Apa30-NH2 such as MR-326 (N-Me-Tyr1, D-Ala2, Arg29, Apa30-NH2-JI-38), and with Gab30-NH2, as MR-502 (D-Ala2, 5F-Phe6, Ser28, Arg29,Gab30-NH2-JI-38) also exhibited much higher potency than JI-38 upon i.v. administration. The relationship between the GH-releasing potency and the analog structure is discussed. Fourteen GHRH agonists with the highest endocrine potencies were subjected to cardiologic tests. MR-409 and MR-356 exhibited higher potency than JI-38 in activating myocardial repair in rats with induced myocardial infarction. As the previous class of analogs, exemplified by JI-38, had shown promising results in multiple fields including cardiology, diabetes and wound healing, our new, more potent, GHRH agonists should manifest additional efficacy for possible medical applications.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
5-aminopentanoyl
Abu
Agm
Apa
Cardioprotection
Dat
EF
Fpa5
GH
GH-releasing hormone
GHRH
Gab
IGF
MI
MeCN
N-Me-Tyr
N-methyl-tyrosine
PKA
PKC
PLC
TOF
acetonitrile
agmatine
des-amino-tyrosine
ejection fraction
gamma-amino-butanoyl
growth hormone
hGHRH agonist
hGHRH(1-29)
human
i.v.
insulin-like growth factor
intravenous, myocardial infarction
pentafluoro-Phe, phospholipase C
protein kinase A
protein kinase C
s.c.
s.c. administration
subcutaneous
time-of-flight
Megjelenés:Peptides. - 52C (2013), p. 104-112. -
További szerzők:Schally, Andrew Victor Cui, Tengjiao Szalontay Luca Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Sha, Wei Kovács Magdolna Jászberényi Miklós He, Jinlin Rick Ferenc G. Popovics Petra Kanashiro-Takeuchi, Rosemeire Hare, Joshua M. Block, Norman L. Zarándi Márta
Pályázati támogatás:TÁMOP-4.2.2.A-11/1/KONV-2012-0025
TÁMOP
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

2.

001-es BibID:BIBFORM033827
035-os BibID:PMID:8875434 WOS:A1996VF15000001
Első szerző:Kovács Magdolna
Cím:Chronic administration of a new potent agonist of growth hormone- releasing hormone induces compensatory linear growth in growth hormone-deficient rats : mechanism of action / Magdolna Kovács, Gábor Halmos, Kate Groot, Jan Izdebski, Andrew V. Schally
Dátum:1996
ISSN:0028-3835
Megjegyzések:To assess the efficacy of a potent agonist analog of GH-releasing hormone (GH-RH), [Dat1,Gln8,Orn12,21,Abu15,Nle27,Asp28,A gm29]hGH-RH(1-29) (JI-38), we investigated the effects of its chronic administration on growth responses in monosodium glutamate (MSG)-lesioned and normal young rats. Body weight (BW), body length (BL), tibia length (TIL), and tail length (TAL) were monitored. Basal serum GH concentrations, GH responses to bolus injections of GH-RH, pituitary GH and serum IGF-I concentrations were measured by RIA. Pituitary GH-RH receptor concentration and binding affinity was also evaluated after the treatment. Neonatal treatment with MSG resulted, as expected, in blunted growth and a decrease in serum and pituitary GH concentration and serum IGF-I levels. A reduction in GH-RH receptor concentration, associated with increased binding affinity of the GH-RH receptor was also found. Chronic administration of GH-RH agonist JI-38 in doses of 2 micrograms at 12-hour intervals for 2 weeks markedly increased the GH responsiveness to GH-RH and stimulated growth, with MSG-treated animals achieving the growth rate of normal controls. Acceleration of growth was associated with stimulated GH synthesis and IGF-I secretion, although basal serum GH levels did not change. Pituitary GH-RH receptor concentration and binding affinity were not significantly modified by the treatment. Treatment of normal young growing rats with agonist JI-38 did not further increase the normal growth acceleration in these rats, but stimulated the GH synthesis and augmented the GH secretory responsiveness. The treatment of MSG-lesioned rats with GH-RH agonist was generally more effective in female than in male animals, and in some cases masked the sex differences in growth rate. Our findings provide the first evidence that the blunted growth rate of the MSG-lesioned rats is associated with a decreased pituitary GH-RH receptor concentration. Our work demonstrates that administration of GH-RH agonist JI-38 is able to restore the normal growth rate of the GH-deficient rats by stimulating GH synthesis and IGF-I secretion.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Neuroendocrinology. - 64 : 3 (1996), p. 169-176. -
További szerzők:Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Izdebski, Jan Schally, Andrew Victor
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

3.

001-es BibID:BIBFORM033817
035-os BibID:PMID:8940358 WOS:A1996VU35100026
Első szerző:Kovács Magdolna
Cím:Effects of acute and chronic administration of a new potent antagonist of growth hormone-releasing hormone in rats : mechanisms of action / Magdolna Kovács, Márta Zarándi, Gábor Halmos, Kate Groot, Andrew V. Schally
Dátum:1996
ISSN:0013-7227
Megjegyzések:Antagonistic analogs of human GH-releasing hormone (hGHRH) are potential candidates for the treatment of disorders characterized by excessive GH secretion and especially for therapy of GH- and insulin-like growth factor (IGF)-dependent tumors. These analogs should be also useful for the studies on the mechanism of action of GHRH. In the present investigation, we evaluated the effects of chronic i.m. administration of a new potent GHRH antagonist (Ibu0,D-Arg2,Phe(4-Cl)6,Abu15,Nle27)hGHRH(1-28)+ ++Agm (MZ-4-71) on the growth rate, serum GH, and IGF-I concentration, GH responsiveness to exogenous GHRH, as well as the pituitary GH content and GHRH receptor concentration in young female rats. We also studied the consequences of acute, high-dose i.v. application of this antagonist on the basal GH and IGF-I levels in adult male rats. In addition, the ability of GHRH antagonist MZ-4-71 to prevent GH release induced by GHRH pulses was determined in vitro in the superfused rat pituitary cell system. Chronic treatment in vivo using twice daily i.m. injections of 20 microg MZ-4-71 for 2 weeks reduced the rate of increase in body weight by 21% and in body length of young rats by 36%, as compared with controls. GH responses to bolus injections of GHRH declined by 22%, and serum IGF-I concentrations by 15% at the end of the treatment. The total pituitary GH content, but not relative GH concentration, also decreased by 15% and GHRH receptor concentration by 48%, following chronic treatment with this antagonist. Bolus injections of high doses of MZ-4-71 (400 microg i.v.) induced a marked and protracted (6 h) inhibition of the basal serum GH concentration and a parallel inhibition of the serum IGF-I levels. The nadir of both the serum GH (62% decrease) and the IGF-I level (30% decrease) was found at 3 h after the injection. In vitro studies showed that MZ-4-71 was able to dose-dependently inhibit the GH-releasing effect of GHRH pulses. Present results demonstrate that GHRH antagonist MZ-4-71 is effective in vivo and that it can inhibit growth and secretion of GH and IGF-I in rats. Our findings also provide new information on the role of GHRH in regulating synthesis of GH and GHRH receptors. It is likely that antagonistic analogs of GHRH could find clinical application for reducing the growth of tumors dependent on GH or IGF-I.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 137 : 12 (1996), p. 5364-5369. -
További szerzők:Zarándi Márta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Schally, Andrew Victor
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

4.

001-es BibID:BIBFORM033697
035-os BibID:WOS:A1996UW79200078
Első szerző:Nagy Attila
Cím:Cytotoxic analogs of luteinizing hormone-releasing hormone containing doxorubicin or 2-pyrrolinodoxorubicin, a derivative 500-1000 times more potent / Attila Nagy, Andrew V. Schally, Patricia Armatis, Karoly Szepeshazi, Gabor Halmos, Magdolna Kovacs, Marta Zarandi, Kate Groot, Masahiro Miyazaki, Andreas Jungwirth, Judit Horvath
Dátum:1996
ISSN:0027-8424
Megjegyzések:Doxorubicin (DOX) and its daunosamine-modified derivative, 2-pyrrolino-DOX, which is 500-1000 times more active than DOX, were incorporated into agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH), The conjugation of DOX with LH-RH analogs was performed by using N-(9-fluorenylmethoxycarbonyl)-DOX-14-O-hemiglutarate, a dicarboxylic acid ester derivative of DOX, Coupling this derivative covalently to the E-amino group of the D-Lys side chain of agonist [D-Lys(6)]LH-RH or antagonistic analog Ac-D-Nal(2)-D-Phe(4Cl)-D-Pal(3)-Ser-Tyr-D-Lys-Leu-Arg-Pro-D-Ala-NH2 [where Nal(2) = 3-(2-naphthyl)alanine, Pal(3) = 3-(3-pyridyl)alanine, and Phe(4Cl) = 4-chlorophenylalanine] was followed by the removal of the 9-fluorenylmethoxycarbonyl protective group to yield cytotoxic derivatives of LH-RH analogs containing DOX, From these DOX containing LH-RH hybrids, intensely potent analogs with daunosamine-modified derivatives of DOX can be readily formed. Thus, cytotoxic LH-RH agonist containing DOX (AN-152) can be converted in a 66% yield by a reaction with a 30-fold excess of 4-iodobutyraldehyde in N,N-dimethylformamide into a derivative having 2-pyrrolino-DOX (AN-207). Hybrid molecules AN-152 and AN-207 fully preserve the cytotoxic activity of their radicals, DOX or 2-pyrrolino-DOX, respectively, in vitro, and also retain the high binding affinity of the peptide hormone portion of the conjugates to rat pituitary receptors for LH-RH, These highly potent cytotoxic analogs of LH-RH were designed as targeted anti-cancer agents for the treatment of various tumors that possess receptors for the carrier peptide, Initial in vivo studies show that the hybrid molecules are much less toxic than the respective cytotoxic radicals incorporated and significantly more active in inhibiting tumor growth.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 93 : 14 (1996), p. 7269-7273. -
További szerzők:Schally, Andrew Victor Armatis, Patricia Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Kovács Magdolna Zarándi Márta Groot, Kate Miyazaki, Masahiro Jungwirth, Andreas Horváth Judit E. (New Orleans)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

5.

001-es BibID:BIBFORM033667
035-os BibID:WOS:000072115900079
Első szerző:Nagy Attila
Cím:Synthesis and biological evaluation of cytotoxic analogs of somatostatin containing doxorubicin or its intensely potent derivative, 2-pyrrolinodoxorubicin / Attila Nagy, Andrew V. Schally, Gábor Halmos, Patricia Armatis, Ren-Zhi Cai, Valér Csernus, Magdolna Kovács, Miklós Koppán, Károly Szepesházi, Zsuzsanna Kahán
Dátum:1998
ISSN:0027-8424
Megjegyzések:To create cytotoxic hybrid analogs of somatostatin (SST), octapeptides RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and RC-121 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NB2) were linked to doxorubicin (DOX) or its superactive derivative, 2-pyrrolino-DOX (AN-201). The conjugation was performed by coupling N-9-fluorenylmethoxycarbonyl (N-Fmoc)-DOX-14-O-hemiglutarate or 2-pyrrolino-DOX-14-O-hemiglutarate to the amino terminus of [Lys(Fmoc)(5)]RC-160 yielding AN-163 and AN-258, respectively, after deprotection. The respective cytotoxic conjugates of RC-121 (AN-162 and AN-238) were prepared similarly, In vitro tests on human cancer cell lines-MKN-45 gastric cancer, MDA-MB-231 breast cancer, PC-3 prostate cancer, and MIA PaCa-2 pancreatic cancer-demonstrated that the antiproliferative activity of the cytotoxic radicals in these conjugates,vas virtually retained. In H-345 human small cell lung carcinoma cell line, conjugates of RC-121 preserved the cytotoxic activity of their radicals, but the hybrids with RC-160 showed approximate to 10 times lower activity. The ability of the carriers and the hybrids to inhibit the binding of I-125-labeled RC-160 to receptors for SST on rat pituitary membrane preparation was also determined. The cytotoxic conjugates inhibited 50% of the specific binding of the radioligand in the nanomolar concentration range (IC50 < 80 nM). When SST-like activities of AN-238 and its carrier, RC-121, were compared in the rat pituitary superfusion system, both compounds were found to suppress a stimulated growth hormone release at nanomolar concentrations. Preliminary studies in animal models of breast and prostate cancers showed that AN-238 is less toxic than AN-201 and more potent in inhibiting tumor growth. These highly active cytotoxic analogs of SST have been designed as targeted antitumor agents for the treatment of various cancers expressing receptors for SST octapeptides.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 95 : 4 (1998), p. 1794-1799. -
További szerzők:Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Armatis, Patricia Cai, Ren-Zhi Csernus Valér J. Kovács Magdolna Koppán Miklós Szepesházi Károly Kahán Zsuzsa
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

6.

001-es BibID:BIBFORM033611
035-os BibID:PMID:11587553 WOS:000171671600001
Első szerző:Schally, Andrew Victor
Cím:Hypothalamic hormones and cancer / Andrew V. Schally, Ana Maria Comaru-Schally, Attila Nagy, Magdolna Kovacs, Karoly Szepeshazi, Artur Plonowski, Jozsef L. Varga, Gabor Halmos
Dátum:2001
ISSN:0091-3022
Megjegyzések:The use of peptide analogs for the therapy of various cancers is reviewed. Inhibition of the pituitary-gonadal axis forms the basis for oncological applications of luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists, but direct effects on tumors may also play a role. Analogs of somatostatin are likewise used for treatment of various tumors. Radiolabeled somatostatin analogs have been successfully applied for the localization of tumors expressing somatostatin receptors. Studies on the role of tumoral LH-RH, growth hormone-releasing hormone (GH-RH), and bombesin/GRP and their receptors in the proliferation of various tumors are summarized, but the complete elucidation of all the mechanisms involved will require much additional work. Human tumors producing hypothalamic hormones are also discussed. Treatment of many cancers remains a major challenge, but new therapeutic modalities are being developed based on antagonists of GH-RH and bombesin, which inhibit growth factors or their receptors. Other approaches consist of the use of cytotoxic analogs of LH-RH, bombesin, and somatostatin, which can be targeted to receptors for these peptides in various cancers and their metastases. These new classes of peptide analogs should lead to a more effective treatment for various cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Frontiers In Neuroendocrinology. - 22 : 4 (2001), p. 248-291. -
További szerzők:Comaru-Schally, Ana Maria Nagy Attila Kovács Magdolna Szepesházi Károly Plonowski, Artur Varga József L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

7.

001-es BibID:BIBFORM058848
Első szerző:Szabó Ildikó
Cím:Comparative in vitro biological evaluation of daunorubicin containing GnRH-I and GnRH-II conjugates developed for tumor targeting / Ildikó Szabó, Szilvia Bősze, Erika Orbán, Éva Sipos, Gábor Halmos, Magdolna Kovács, Gábor Mező
Dátum:2015
ISSN:1075-2617
Megjegyzések:Hormone based drug targeting is a promising tool for selective tumor therapy. In this study, synthesis and systematic comparative biological evaluation of novel drug containing analogs of gonadotropin-releasing hormone GnRH-I and GnRH-II is reported demonstrating their suitability for tumor targeting. The cytotoxic conjugates were prepared by the attachment of the chemotherapeutical agent daunorubicin (Dau) to GnRH analogs directly or through an enzyme-labile spacer with oxime linkage. All conjugates were found to be proteolytically stable under circumstances applied in biological assays. Both GnRH-I and GnRH-II were able to bind similarly to high-affinity GnRH-I receptors on human pituitary and human prostate cancer cells. The in vitro long-term cytotoxic effect of the conjugates was comparable with that of the free drug in human breast and colon cancer cell lines. Furthermore, a concentration-dependent cellular uptake profile was observed. The in vitro apoptotic effect of the compounds was evaluated by flow cytometry analysis using annexin-V. Our results show that both the GnRH-I and the GnRH-II based analogs might be applied for targeted tumor therapy. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
targeted tumor therapy
gonadotropin-releasing hormone
targeting unit
receptor binding affinity
long-term cytotoxic effect
apoptotic effect
Megjelenés:Journal Of Peptide Science. - 21 : 5 (2015), p. 426-435. -
További szerzők:Bősze Szilvia Orbán Erika Sipos Éva (1989-) (gyógyszerész) Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Kovács Magdolna Mező Gábor (1959-) (vegyész)
Pályázati támogatás:4.2.2.A-11/1/KONV-2012-0025
TÁMOP
K81596
OTKA
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

8.

001-es BibID:BIBFORM033756
035-os BibID:(WoS)000071848300008 (Scopus)0031913859 (PMID)9516049
Első szerző:Tóth Katalin
Cím:New analogs of human growth hormone-releasing hormone (1-29) with high and prolonged antagonistic activity / Katalin Toth, Magdolna Kovacs, Marta Zarandi, Gabor Halmos, Kate Groot, Attila Nagy, Zoltan Kele, Andrew V. Schally
Dátum:1998
ISSN:1397-002X 1399-3011
Megjegyzések:Based on our previous results, in conjunction with various structural considerations, 19 new analogs of the GHRH antagonist [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Abu15,Nle27,Agm29]++ +hGHRH(1-29) (MZ-5-156) were synthesized by the solid-phase method. These compounds were designed to develop further analogs of this class with increased receptor-binding affinity. All analogs had Abu15 and Nle27 modifications and were acylated with phenylacetic acid at the N-terminus. Most of the analogs had D-Arg2 and Phe(pCl)6 substituents and Agm29 or Arg29-NH2 at the C-terminus. Additional single substitutions consisted of the incorporation of D- or L-Tic1, D-Tic2, Tic6 or Phe(pNO2)6 and Arg29-NH2. The Arg29-NH2 analog of MZ-5-156 (KT-48) was further modified by single substitutions using Pal1; D-Tpi2; D- or L-Phe4; Phe(pX)6 X = F, Cl, I; Tyr7; Aib8; Tyr(Me)10 or Phe(pCl)10. Four peptides had multiple substitutions. All the analogs were evaluated for their ability to inhibit GH release induced by hGHRH(1-29)NH2 in vitro and some were also tested in vivo. Peptides [PhAc-Tyr1,D-Arg2,Phe(pI)6,Abu15,Nle27]hGHRH(1-2 9)NH2 (KT-30), [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Aib8,Abu15,Nle27] hGHRH(1-29)NH2 (KT-50) and [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Tyr(Me)10,Abu15,Nle27]h GHRH(1-29)NH2 (KT-40) with Phe(pI)6, Aib8 or Tyr(Me)10 modifications, respectively, showed high and prolonged inhibitory effect in superfused rat pituitary system. Analog KT-50 also exhibited a strong and long-term inhibitory activity in vivo in rats. Most of the new analogs showed high binding affinities to rat pituitary GHRH receptors.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
külföldön készült közlemény
Megjelenés:The journal of peptide research. - 51 : 2 (1998), p. 134-141. -
További szerzők:Kovács Magdolna Zarándi Márta Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Nagy Attila Kele Zoltán Schally, Andrew Victor
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

9.

001-es BibID:BIBFORM033591
035-os BibID:WOS:000188921200052
Első szerző:Varga József L.
Cím:Increased activity of antagonists of growth hormone-releasing hormone substituted at positions 8, 9, and 10 / Jozsef L. Varga, Andrew V. Schally, Judit E. Horvath, Magdolna Kovacs, Gabor Halmos, Kate Groot, Gabor L. Toller, Zoltan Rekasi, Marta Zarandi
Dátum:2004
ISSN:0027-8424
Megjegyzések:Antagonists of human growth hormone-releasing hormone (hGHRH) with increased potency and improved enzymatic and chemical stability are needed for potential clinical applications. We synthesized 21 antagonistic analogs of hGHRH(1-29)NH2, substituted at positions 8, 9, and 10 of the common core sequence {phenylacetyl-Tyr1, D-Arg(2,28), para-chloro-phenylalanine 6, Arg(9)/homoarginine 9, Tyr(10)/O-methyltyrosine 10, alpha-aminobutyric acid 15, norleucine 27, Har(29)} hGHRH(1-29)NH2. Inhibitory effects on hGHRH-induced GH release were evaluated in vitro in a superfused rat pituitary system, as well as in vivo after i.v. injection into rats. The binding affinities of the peptides to pituitary GHRH receptors were also determined. Introduction of para-amidinophenylalanine 10 yielded antagonists JV-1-62 and -63 with the highest activities in vitro and lowest receptor dissociation constants (K-i = 0.057-0.062 nM). Antagonists JV-1-62 and -63 also exhibited the strongest effect in vivo, significantly (P < 0.05-0.001) inhibiting hGHRH-induced GH release for at least 1 h. Para-aminopherylalanine 10 and O-ethyltyrosine 10 substitutions yielded antagonists potent in vitro, but His(10), 3,3'-diphenylalanine 10, 2-naphthylalanine 10,and cyclohexylalanine 10 modifications were detrimental. Antagonists containing citrulline 9 (in MZ-J-7-72), amidinophenylalanine 9 (in JV-1-65), HiS(9), D-Arg(9), citrulline 8, AIa(8), D-Ala(8), or alpha-aminobutyric acid 8 substituents also had high activity and receptor affinity in vitro. However, in vitro potencies of analogs with substitution in position 9 correlated poorly with acute endocrine effects in vivo, as exemplified by the weak and/or short inhibitory actions of antagonists JV-1-65 and MZ-J-7-72 on GH release in vivo. Nevertheless, antagonist JV-1-65 was more potent than JV-1-63 in tests on inhibition of the growth of human prostatic and lung cancer lines xenografted into nude mice. This indicates that oncological activity may be based on several mechanisms. hGHRH antagonists with improved efficacy could be useful for treatment of cancers that depend on insulin-like growth factors or GHRH.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 101 : 6 (2004), p. 1708-1713. -
További szerzők:Schally, Andrew Victor Horváth Judit E. (New Orleans) Kovács Magdolna Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Toller Gábor L. Rékási Zoltán Zarándi Márta
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

10.

001-es BibID:BIBFORM072409
Első szerző:Zarándi Márta
Cím:Synthesis and structure-activity studies on novel analogs of human growth hormone releasing hormone (GHRH) with enhanced inhibitory activities on tumor growth / Marta Zarandi, Renzhi Cai, Magdolna Kovacs, Petra Popovics, Luca Szalontay, Tengjiao Cui, Wei Sha, Miklos Jaszberenyi, Jozsef Varga, XianYang Zhang, Norman L. Block, Ferenc G. Rick, Gabor Halmos, Andrew V. Schally
Dátum:2017
ISSN:0196-9781
Megjegyzések:The syntheses and biological evaluations of new GHRH analogs of Miami (MIA) series with greatly increased anticancer activity are described. In the design and synthesis of these analogs, the following previous substitutions were conserved: D-Arg(2), Har(9), Abuls(15), and Nle(27). Most new analogs had Ala at position 8. Since replacements of both Lys(12) and Lys(21) with Orn increased resistance against enzymatic degradation, these modifications were kept. The substitutions of Arg at both positions 11 and 20 by His were also conserved. We kept D-Arg(28), Har(29) -NH2 at the C-terminus or inserted Agm or 12-amino dodecanoic acid amide at position 30. We incorporated pentafluoro-Phe (Fpa(s)), instead of Cpa, at position 6 and Tyr(Me) at position 10 and omega-amino acids at N-terminus of some analogs. These GHRH analogs were prepared by solid-phase methodology and purified by HPLC. The evaluation of the activity of the analogs on GH release was carried out in vitro on rat pituitaries and in vivo in male rats. Receptor binding affinities were measured in vitro by the competitive binding analysis. The inhibitory activity of the analogs on tumor proliferation in vitro was tested in several human cancer cell lines such as HEC-1A endometrial adenocarcinoma, HCT-15 colorectal adenocarcinoma, and LNCaP prostatic carcinoma. For in vivo tests, various cell lines including PC-3 prostate cancer, HEC-1A endometrial adenocarcinoma, HT diffuse mixed beta cell lymphoma, and ACHN renal cell carcinoma cell lines were xenografted into nude mice and treated subcutaneously with GHRH antagonists at doses of 1-5 mu g/day. Analogs MIA-602, MIA-604, MIA-610, and MIA-640 showed the highest binding affinities, 30, 58, 48, and 73 times higher respectively, than GHRH (1-29) NH2. Treatment of LNCaP and HCT-15 cells with 5 mu M MIA-602 or MIA-690 decreased proliferation by 40%-80%. In accord with previous tests in various human cancer lines, analog MIA-602 showed high inhibitory activity in vivo on growth of PC-3 prostate cancer, HT-mixed beta cell lymphoma, HEC-1A endometrial adenocarcinoma and ACHN renal cell carcinoma. Thus, GHRH analogs of the Miami series powerfully suppress tumor growth, but have only a weak endocrine GH inhibitory activity. The suppression of tumor growth could be induced in part by the downregulation of GHRH receptors levels. Published by Elsevier Inc.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Peptides. - 89 (2017), p. 60-70. -
További szerzők:Cai, Ren-Zhi Kovács Magdolna Popovics Petra Szalontay Luca Cui, Tengjiao Sha, Wei Jászberényi Miklós Varga József XianYang, Zhang Block, Norman L. Rick Ferenc G. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Schally, Andrew Victor
Internet cím:DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

11.

001-es BibID:BIBFORM033541
035-os BibID:WOS:000236362600052
Első szerző:Zarándi Márta
Cím:Lipopeptide antagonists of growth hormone-releasing hormone with improved antitumor activities / Marta Zarandi, Jozsef L. Varga, Andrew V. Schally, Judit E. Horvath, Gabor L. Toller, Magdolna Kovacs, Markus Letsch, Kate Groot, Patricia Armatis, Gabor Halmos
Dátum:2006
ISSN:0027-8424
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) synthesized previously inhibit proliferation of various human cancers, but derivatisation with fatty acids could enhance their clinical efficacy. We synthesized a series of antagonists of GHRH(1-29)NH2 acylated at the N terminus with monocarboxylic or alpha,omega-dicarboxylic acids containing six to sixteen carbon atoms. These peptides are analogs of prior potent antagonists JV-1-36, JV-1-38, and JV-1-65 with phenylacetyl group at their N terminus. Several new analogs, including MZ-J-7-46 and MZA-7-30, more effectively inhibited GHRH-induced GH release in vitro in a superfused rat pituitary system than their parent compound JV-1-36 and had increased binding affinities to rat pituitary GHRH receptors, but they showed weaker inhibition of GH release in vivo than JV-1-36. All antagonists acylated with fatty acids containing 8-14 carbon atoms inhibited the proliferation of MiaPaCa-2 human pancreatic cancer cells in vitro better than JV-1-36 or JV-1-65. GHRH antagonist MZ-J-7-114 (5 mu g/day) significantly suppressed the growth of PC-3 human androgen-independent prostate cancers xenografted into nude mice and reduced serum lGF-I levels, whereas antagonist JV-1-38 had no effect at the dose of 10 mu g/day. GHRH antagonists including MZ-J-7-46 and MZ-J-7-114 acylated with octanoic acid and MZ-J-7-30 and MZ-J-7-110 acylated with 1,12-dodecanedicarboxylic acid represent relevant improvements over earlier antagonists. These and previous results suggest that this class of GHRH antagonists might be effective in the treatment of various cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 103 : 12 (2006), p. 4610-4615. -
További szerzők:Varga József L. Schally, Andrew Victor Horváth Judit E. (New Orleans) Toller Gábor L. Kovács Magdolna Letsch, Markus Groot, Kate Armatis, Patricia Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

001-es BibID:BIBFORM033755
Első szerző:Zarándi Márta
Cím:Synthesis and in vitro biological activities of new potent GH-RH antagonists with citrulline substitutions / Márta Zarándi, Magdolna Kovács, Judit E. Horváth, Gábor Halmos, Kate Groot, Andrew V. Schally
Dátum:1998
ISSN:0196-9781
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok előadáskivonat
Megjelenés:Peptides 1996 : Proceedings of the Twenty-Fourth European Peptide Symposium, September 8-13, 1996, Edinburg, Scotland / eds. by Robert Ramage, Roger Epton. - p. 933-934.
További szerzők:Kovács Magdolna Horváth Judit E. (New Orleans) Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Schally, Andrew Victor
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
Borító:
Rekordok letöltése1 2