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Article: Targeted Glioma Therapy-Clinical Trials and Future Directions.

Shikalov, Aleksandr / Koman, Igor / Kogan, Natalya M

2024 Volume 16, Issue 1

Abstract: Glioblastoma multiforme (GBM) is the most common type of glioma, with a median survival of 14.6 months post-diagnosis. Understanding the molecular profile of such tumors allowed the development of specific targeted therapies toward GBM, with a major role ...

Abstract	Glioblastoma multiforme (GBM) is the most common type of glioma, with a median survival of 14.6 months post-diagnosis. Understanding the molecular profile of such tumors allowed the development of specific targeted therapies toward GBM, with a major role attributed to tyrosine kinase receptor inhibitors and immune checkpoint inhibitors. Targeted therapeutics are drugs that work by specific binding to GBM-specific or overexpressed markers on the tumor cellular surface and therefore contain a recognition moiety linked to a cytotoxic agent, which produces an antiproliferative effect. In this review, we have summarized the available information on the targeted therapeutics used in clinical trials of GBM and summarized current obstacles and advances in targeted therapy concerning specific targets present in GBM tumor cells, outlined efficacy endpoints for major classes of investigational drugs, and discussed promising strategies towards an increase in drug efficacy in GBM.
Language	English
Publishing date	2024-01-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics16010100
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cannabinoid Quinones-A Review and Novel Observations.

Kogan, Natalya M / Peters, Maximilian / Mechoulam, Raphael

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 6

Abstract: A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism ... ...

Abstract	A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase IIα catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.
MeSH term(s)	Animals ; Cannabidiol/analogs & derivatives ; Cannabidiol/chemistry ; Cannabidiol/therapeutic use ; DNA Topoisomerases, Type II/metabolism ; Humans ; Mice ; Mice, Nude ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasm Proteins/metabolism ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/enzymology ; Poly-ADP-Ribose Binding Proteins/antagonists & inhibitors ; Poly-ADP-Ribose Binding Proteins/metabolism ; Quinones/chemistry ; Quinones/therapeutic use ; Topoisomerase II Inhibitors/chemistry ; Topoisomerase II Inhibitors/therapeutic use
Chemical Substances	Neoplasm Proteins ; Poly-ADP-Ribose Binding Proteins ; Quinones ; Topoisomerase II Inhibitors ; cannabidiol hydroxyquinone (137252-25-6) ; Cannabidiol (19GBJ60SN5) ; DNA Topoisomerases, Type II (EC 5.99.1.3) ; TOP2A protein, human (EC 5.99.1.3)
Language	English
Publishing date	2021-03-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26061761
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Article ; Online: Cannabinoid Quinones—A Review and Novel Observations

Natalya M. Kogan / Maximilian Peters / Raphael Mechoulam

Molecules, Vol 26, Iss 1761, p

2021 Volume 1761

Abstract	A cannabinoid anticancer para-quinone, HU-331, which was synthesized by our group five decades ago, was shown to have very high efficacy against human cancer cell lines in-vitro and against in-vivo grafts of human tumors in nude mice. The main mechanism was topoisomerase IIα catalytic inhibition. Later, several groups synthesized related compounds. In the present presentation, we review the publications on compounds synthesized on the basis of HU-331, summarize their published activities and mechanisms of action and report the synthesis and action of novel quinones, thus expanding the structure-activity relationship in these series.
Keywords	cannabinoid ; quinones ; anti-cancer ; structure-activity relationship ; Organic chemistry ; QD241-441
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Endocannabinoid basis of personality-Insights from animal model of social behavior.

Kogan, Natalya M / Begmatova, Dilorom / Vinnikova, Liudmila / Malitsky, Sergey / Itkin, Maxim / Sharon, Eyal / Klinov, Artem / Gorelick, Jonathan / Koman, Igor / Vogel, Zvi / Mechoulam, Raphael / Pinhasov, Albert

Frontiers in pharmacology

2023 Volume 14, Page(s) 1234332

Abstract: Rationale: ...

Abstract	Rationale:
Language	English
Publishing date	2023-08-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1234332
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Article: Case report: Preimplantation genetic testing for infantile GM1 gangliosidosis.

Zagaynova, Valeria A / Nasykhova, Yulia A / Tonyan, Ziravard N / Danilova, Maria M / Dvoynova, Natalya M / Lazareva, Tatyana E / Ivashchenko, Tatyana E / Shabanova, Elena S / Krikheli, Inna O / Lesik, Elena A / Bespalova, Olesya N / Kogan, Igor Yu / Glotov, Andrey S

Frontiers in genetics

2024 Volume 15, Page(s) 1344051

Abstract: Ganglioside-monosialic acid (GM1) gangliosidosis (ICD-10: E75.1; OMIM: 230500, 230600, 230650) is a rare autosomal recessive hereditary disease, lysosomal storage disorder caused by mutations in ... ...

Abstract	Ganglioside-monosialic acid (GM1) gangliosidosis (ICD-10: E75.1; OMIM: 230500, 230600, 230650) is a rare autosomal recessive hereditary disease, lysosomal storage disorder caused by mutations in the
Language	English
Publishing date	2024-02-09
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2024.1344051
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Article ; Online: Cannabinoid Receptor 2 Blockade Prevents Anti-Depressive-like Effect of Cannabidiol Acid Methyl Ester in Female WKY Rats.

Hen-Shoval, Danielle / Moshe, Lital / Indig-Naimer, Talia / Mechoulam, Raphael / Shoval, Gal / Zalsman, Gil / Kogan, Natalya M / Weller, Aron

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: The pathophysiology of major depressive disorder (MDD) is diverse and multi-factorial, yet treatment strategies remain limited. While women are twice as likely to develop the disorder as men, many animal model studies of antidepressant response rely ... ...

Abstract	The pathophysiology of major depressive disorder (MDD) is diverse and multi-factorial, yet treatment strategies remain limited. While women are twice as likely to develop the disorder as men, many animal model studies of antidepressant response rely solely on male subjects. The endocannabinoid system has been linked to depression in clinical and pre-clinical studies. Cannabidiolic Acid-Methyl Ester (CBDA-ME, EPM-301) demonstrated anti-depressive-like effects in male rats. Here, we explored acute effects of CBDA-ME and some possible mediating mechanisms, using a depressive-like genetic animal model, the Wistar-Kyoto (WKY) rat. In Experiment 1, Female WKY rats underwent the Forced swim test (FST) following acute CBDA-ME oral ingestion (1/5/10 mg/kg). In Experiment 2, Male and female WKY rats underwent the FST after injection of CB1 (AM-251) and CB2 (AM-630) receptor antagonists 30 min before acute CBDA-ME ingestion (1 mg/kg, males; 5 mg/kg, females). Serum levels of Brain-Derived Neurotrophic Factor (BDNF), numerous endocannabinoids and hippocampal Fatty Acid Amide Hydrolase (FAAH) levels were assessed. Results indicate that females required higher doses of CBDA-ME (5 and 10 mg/kg) to induce an anti-depressive-like effect in the FST. AM-630 blocked the antidepressant-like effect in females, but not in males. The effect of CBDA-ME in females was accompanied by elevated serum BDNF and some endocannabinoids and low hippocampal expression of FAAH. This study shows a sexually diverse behavioral anti-depressive response to CBDA-ME and possible underlying mechanisms in females, supporting its potential use for treating MDD and related disorders.
MeSH term(s)	Animals ; Female ; Male ; Rats ; Brain-Derived Neurotrophic Factor ; Cannabidiol/therapeutic use ; Depressive Disorder, Major/drug therapy ; Disease Models, Animal ; Endocannabinoids ; Rats, Inbred WKY ; Receptor, Cannabinoid, CB2/antagonists & inhibitors
Chemical Substances	Brain-Derived Neurotrophic Factor ; Cannabidiol (19GBJ60SN5) ; cannabidiolic acid (FJX8O3OJCD) ; Endocannabinoids ; Cnr2 protein, rat ; Receptor, Cannabinoid, CB2
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043828
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Article ; Online: Novel Synthesis of C-Methylated Phytocannabinoids Bearing Anti-inflammatory Properties.

Lavi, Yarden / Kogan, Natalya M / Topping, Louise M / Liu, Caojie / McCann, Fiona E / Williams, Richard O / Breuer, Aviva / Yekhtin, Zhanna / Ezra, Aviva Friedman / Gallily, Ruth / Feldmann, Marc / Mechoulam, Raphael

Journal of medicinal chemistry

2023 Volume 66, Issue 8, Page(s) 5536–5549

Abstract: There is growing interest in non-psychoactive phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), and cannabichromene, as potential leads for novel therapeutic agents. In this study, we report on the development of new derivatives in which ... ...

Abstract	There is growing interest in non-psychoactive phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), and cannabichromene, as potential leads for novel therapeutic agents. In this study, we report on the development of new derivatives in which we methylated either position 4 of olivetol or the phenolic positions of olivetol, or both. We introduce a refinement on previously reported chemical procedures for phytocannabinoid derivatization as well as the biological evaluation of all derivatives in anti-inflammatory in vivo models. Compounds such as the CBD derivative,
MeSH term(s)	Cannabidiol/pharmacology ; Resorcinols ; Anti-Inflammatory Agents ; Cytokines
Chemical Substances	olivetol (65OP0NEZ1P) ; Cannabidiol (19GBJ60SN5) ; Resorcinols ; Anti-Inflammatory Agents ; Cytokines
Language	English
Publishing date	2023-04-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c01988
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Beyond THC and Endocannabinoids.

Pacher, Pal / Kogan, Natalya M / Mechoulam, Raphael

Annual review of pharmacology and toxicology

2019 Volume 60, Page(s) 637–659

Abstract: Research in the cannabinoid field, namely on phytocannabinoids, the endogenous cannabinoids anandamide and 2-arachidonoyl glycerol and their metabolizing and synthetic enzymes, the cannabinoid receptors, and anandamide-like cannabinoid compounds, has ... ...

Abstract	Research in the cannabinoid field, namely on phytocannabinoids, the endogenous cannabinoids anandamide and 2-arachidonoyl glycerol and their metabolizing and synthetic enzymes, the cannabinoid receptors, and anandamide-like cannabinoid compounds, has expanded tremendously over the last few years. Numerous endocannabinoid-like compounds have been discovered. The Cannabis plant constituent cannabidiol (CBD) was found to exert beneficial effects in many preclinical disease models ranging from epilepsy, cardiovascular disease, inflammation, and autoimmunity to neurodegenerative and kidney diseases and cancer. CBD was recently approved in the United States for the treatment of rare forms of childhood epilepsy. This has triggered the development of many CBD-based products for human use, often with overstated claims regarding their therapeutic effects. In this article, the recently published research on the chemistry and biological effects of plant cannabinoids (specifically CBD), endocannabinoids, certain long-chain fatty acid amides, and the variety of relevant receptors is critically reviewed.
MeSH term(s)	Animals ; Arachidonic Acids/metabolism ; Cannabinoid Receptor Agonists/pharmacology ; Cannabinoids/pharmacology ; Dronabinol/pharmacology ; Endocannabinoids/metabolism ; Glycerides/metabolism ; Humans ; Polyunsaturated Alkamides/metabolism
Chemical Substances	Arachidonic Acids ; Cannabinoid Receptor Agonists ; Cannabinoids ; Endocannabinoids ; Glycerides ; Polyunsaturated Alkamides ; Dronabinol (7J8897W37S) ; glyceryl 2-arachidonate (8D239QDW64) ; anandamide (UR5G69TJKH)
Language	English
Publishing date	2019-10-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	196587-6
ISSN	1545-4304 ; 0362-1642
ISSN (online)	1545-4304
ISSN	0362-1642
DOI	10.1146/annurev-pharmtox-010818-021441
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Age-Related COVID-19 Influence on Male Fertility.

Shcherbitskaia, Anastasiia D / Komarova, Evgeniia M / Milyutina, Yulia P / Sagurova, Yanina M / Ishchuk, Mariia A / Mikhel, Anastasiia V / Ob'edkova, Ksenia V / Lesik, Elena A / Gzgzyan, Alexander M / Tapilskaya, Natalya I / Bespalova, Olesya N / Kogan, Igor Y

International journal of molecular sciences

2023 Volume 24, Issue 21

Abstract: The impact of coronavirus on the reproductive health of men attracts the special attention of many researchers. While studies suggest changes in sperm parameters and the possibility of testicular inflammation, further studies are needed to elucidate any ... ...

Abstract	The impact of coronavirus on the reproductive health of men attracts the special attention of many researchers. While studies suggest changes in sperm parameters and the possibility of testicular inflammation, further studies are needed to elucidate any potential age-related changes in these findings, which is the purpose of the present study. The semen quality parameters, cytokine concentration, and markers of the pro- and antioxidant system were assessed in 60 men five to seven months after the coronavirus infection and in 77 controls (without a history of coronavirus infection). Additionally, participants were divided into two age groups: less than 35 years and 35 years or older. Notably increased round cell count in ejaculate and reduced sperm hyaluronan binding ability were observed among post-infection patients younger than 35 years. In the same group, a decline in seminal plasma zinc levels and nitrotyrosine in the cell fraction was found. In men over 35 years of age, Coronavirus Disease 2019 (COVID-19) led to increased sperm DNA fragmentation, a decrease in the total antioxidant capacity, and an elevation in the levels of interleukin-1β and interleukin-10. The concentration of interleukin-1β decreased over time following recovery in all affected patients. The data obtained suggest the potential adverse impact of the coronavirus infection on male reproductive health; however, these effects appear to be age-dependent.
MeSH term(s)	Humans ; Male ; Adult ; Semen Analysis ; Infertility, Male/etiology ; Infertility, Male/metabolism ; Semen/metabolism ; Interleukin-1beta/metabolism ; Sperm Count ; Antioxidants/metabolism ; COVID-19/metabolism ; Spermatozoa/metabolism ; Fertility ; Sperm Motility
Chemical Substances	Interleukin-1beta ; Antioxidants
Language	English
Publishing date	2023-10-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242115742
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Article ; Online: Vaginal Microbiota Molecular Profiling in Women with Bacterial Vaginosis: A Novel Diagnostic Tool.

Savicheva, Alevtina M / Krysanova, Anna A / Budilovskaya, Olga V / Spasibova, Elena V / Khusnutdinova, Tatiana A / Shalepo, Kira V / Beliaeva, Natalia R / Safarian, Galina Kh / Sapozhnikov, Kirill V / Tapilskaya, Natalya I / Kogan, Igor Yu

International journal of molecular sciences

2023 Volume 24, Issue 21

Abstract: Bacterial vaginosis (BV) is a most common microbiological syndrome. Multiplex next-generation sequencing (NGS) or molecular tests allow a complete and accurate vaginal microbiota profiling in order to determine the primary causative agent. Due to the ... ...

Abstract	Bacterial vaginosis (BV) is a most common microbiological syndrome. Multiplex next-generation sequencing (NGS) or molecular tests allow a complete and accurate vaginal microbiota profiling in order to determine the primary causative agent. Due to the high costs and limited availability of NGS, the multiplex real-time PCR draws more attention. The present study aimed to evaluate the microbial composition and dominant lactobacilli species in non-pregnant women with bacterial vaginosis using a multiplex RT-PCR test and determine its diagnostic significance. In total, 331 women complaining of vaginal discharge were included. BV was confirmed upon clinical examination and Nugent criteria. A real-time PCR test was carried out with a new Femoflor test, which identifies opportunistic bacteria, STD pathogens, and some viruses. According to the results, the rate of lactobacilli is significantly reduced in BV-affected patients when compared to healthy women. Moreover, the rate of
MeSH term(s)	Female ; Humans ; Gardnerella vaginalis/genetics ; Lactobacillus/genetics ; Microbiota/genetics ; Vagina/microbiology ; Vaginosis, Bacterial/diagnosis ; Vaginosis, Bacterial/microbiology
Language	English
Publishing date	2023-11-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242115880
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