Shotaro Goto's research while affiliated with Fukuoka University and other places
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Publications (14)
Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test...
Epidermal growth factor receptor (EGFR) inhibitors frequently cause severe skin rash as a side effect, which is a critical burden for patients who continuously receive drug treatments. Several recent clinical trials have shown that vitamin K is effective against these side effects; however, the underlying mechanisms remain unclear. EGFR inhibitors...
Purpose
Although curcumin (Cur) has powerful pharmacological effects, its use in medicine has not been established yet. The oral bioavailability (BA) of Cur is limited because of its poor water solubility. The purpose of this study was to confirm whether cationic N,N-dimethyl amino acid esters of Cur could act as prodrugs and improve its water solu...
Mitochondria generate energy through the action of the electron transport chain (ETC) and ATP synthase. Mitochondrial malfunction can lead to various disorders, including neurodegenerative diseases. Several reports have shown that menaquinone-4 (MK-4, vitamin K2(20)), a safe drug for osteoporosis, may improve mitochondrial function. Here, we hypoth...
The intestinal absorption of hydrophobic compounds is severely influenced by their transportation rate through the unstirred water layer in the intestinal lumen. A member of the vitamin E family, α-Tocotrienol (α-T3) has remarkable pharmacological effects, but its intestinal absorption is hampered due to its hydrophobicity. Here, we prepared three...
Topical application of vitamin K is beneficial in the treatment of various skin pathologies. However, its delivery to the skin is hampered by the photo-instability and phototoxicity of vitamin K (quinone form). Indeed, topical use of vitamin K is regulated in Europe owing to the photosensitive properties of this molecule. Here, we discuss the suita...
The first-choice drug for acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA), frequently causes drug-resistance and some adverse effects. Thus, an effective and safe agent for ATRA-resistant APL is needed. Menaquinone-4 (MK-4, vitamin K2(20)), used for osteoporosis treatment, does not have serious adverse effects. It has been report...
Ubiquinol-10 (UqH-10), the fully reduced form of ubiquinone-10 (Uq-10, coenzyme Q10 ), is an antioxidant and is involved in energy production. However, physicochemical disadvantages, such as rapid oxidation, water-insolubility, photoinstability, and phototoxicity, limit its application. We previously reported that UqH-10 1,4-bis-N,N-dimethylglycina...
Schizophrenia is a severe, chronic mental illness characterized by delusions, hallucinations, negative symptoms, and cognitive dysfunction. Recently, several studies have demonstrated that the pathogenesis of schizophrenia involves mitochondrial dysfunction and oxidative stress. However, the effect of antipsychotic drugs for these events has been p...
Topical application of phylloquinone (PK) is beneficial to the skin; however, its topical use is limited in Europe owing to its photosensitive properties such as photodegradation and phototoxicity. We evaluated the suitability of ester derivatives of phyllohydroquinone (PKH), the active form of PK, for topical application to overcome the abovementi...
The effective delivery of menahydroquinone-4 (MKH), an active form of menaquinone-4 (MK-4, vitamin K2(20)), to the skin is beneficial in the treatment of various skin pathologies. However, its delivery through the application of MK-4 to the skin is hampered due to the photoinstability and phototoxicity of MK-4. This study aimed to evaluate the pote...
Hepatocellular carcinoma (HCC) shows poor prognosis owing to its very frequent recurrence even after curative treatment. Thus, an effective and safe long-term chemopreventive agent is strongly in demand. Menahydroquinone-4 (MKH) is an active form of menaquinone-4 (MK-4, vitamin K2) that is involved in the synthesis of vitamin K-dependent proteins i...
Citations
... Many amino acid conjugates of Cur have been reported by Parvathy et al. to evaluate their antioxidant and antimutagenic effects [35]. Based on our previous work and experience [36,37], we selected the other cationic N,N-dimethyl amino acid prodrugs ( Fig. 1) and evaluated their water solubility, regeneration profile to parent form (Cur) in rat and human microsomes, oral BA in rats, and anti-inflammatory effects in macrophage RAW 264.7 stimulated with lipopolysaccharide (LPS). ...
... Due to the similarities between cancer immune response and the coronavirus disease 2019 (COVID-19), a list of drugs that have been approved for cancer indication by the US FDA has entered clinical trials for COVID-19 treatments [29]. In the same line of thought, ester derivatives of menahydroquinone-4, used for osteoporosis treatment, were shown to exert strong growth-inhibitory effects on all-trans retinoic acid (ATRA)-resistant acute promyelocytic leukemia cells [30]. ...
Reference: Novel Anticancer Strategies II
... It is reported that CoQ10 and CoQ10H2 undergo degradation upon UV irradiation 33 . In addition to the isomeric peak, a number of additional peaks were observed in TIC and mass spectra of irradiated CoQ10 (Fig. S4, Fig. S6, Fig. S9), suggesting some other phenomena (that may include the degradation and dimerization of CoQ10) has also occurred upon irradiation. ...
... INTRODUCTION Ziprasidone ( Fig. 1.), which is the benzisothiazolpiperazinyl (BITP) derivative, is an atypical (second-generation) antipsychotic drug, which has a unique G protein coupled receptor (GPCR) binding profile [1]. Ziprasidone has very high affinity to the 5HT 2A and 5HT 2C receptors and to the 5HT 1B , 5HT 1D , 5HT 7 , a 1B , D 2 , D 3 sites, and a moderate affinity to the 5HT 1A , 5HT 2B , 5HT 5 , 5HT 6 , a 1A , a 2A , a2B, a 2C , D 1 , D 4 and H 1 receptors. Its indication is for treatment of positive, negative and affective symptoms of schizophrenia, with a relatively low incidence of extrapyramidal side effects [2]. ...
... As a result, the full potential of PK cannot be realized. Furthermore, it is also conceivable that PK exhibits lower cellular uptake and has lower bioavailability than MK-4, contributing to its ineffectiveness on CCL5 expression 18,37 . ...
... Therefore, we hypothesized that adequate MKH delivery to the skin may suppress EGFR inhibitor-induced skin rashes. We previously reported that ester-type derivatives ( Fig. 1) menahydroquinone-4 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG) and menahydroquinone-4 1,4-bis-hemisuccinate (MKH-SUC) deliver MKH to skin cells more efficiently than MK-4 18 . Furthermore, MKH derivatives are more suitable for skin use because of their higher photostability than MK-4. ...
... It has been reported that MK-4 induces apoptosis via the activation of BAK, a member of the Bcl-2 family of apoptosis-promoting proteins, indicating an interaction between MKO and BAK [12]. Previously, we reported that the MKH ester derivatives 1,4-bis-N,N-dimethylglycinate (MKH-DMG) and 1,4-bis-hemi-succinate (MKH-SUC) ( Figure 1A) act as prodrugs for hepatocellular carcinoma (HCC) cells, and exhibit strong antitumor effects compared with MK-4 [17,18]. As MKH is the active form of MK-4, in terms of the physiological effects, such as blood coagulation and bone formation, MKH may contribute to the inhibitory effect of MK-4. ...
