Pub Date : 2023-01-01DOI: 10.4236/ojmc.2023.132002
Abiodun S. Oyedele, Toluwase H. Fatoki, Esha Dalvie, Neil Osheroff, Cosmas O. Okoro
Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize and computationally evaluate pharmacological potential of some derivatives of 9-amino-3-phenylacridone, as topoisomerase II (Topo II) inhibitors. In this study, 10 derivatives of 3-phenyl-9-aminoacridone were chemically synthesized and characterized, and the potential pharmacological indications of these compounds were computationally predicted by methods such as ADMET prediction, molecular target prediction and molecular docking. The results showed that two derivatives (58e and 58j) were non-permeant of blood-brain barrier, and this property was found similar to that of amsacrine and etoposide. The results of molecular docking of the ten derivatives of 3-phenyl-9-aminoacridone that were synthesized in this work showed that the synthetic compounds (58a-j) and the standard drugs have overall best binding affinities for human acetylcholine esterase than butyrylcholinesterase, and overall best binding affinities for human topo IIα than human topo IIβ. Overall, the results of this study suggest that the synthetic compounds 58a, 58c, 58f, 58g, and 58i could probably inhibit topo IIα by catalytic inhibition as seen with amsacrine, but only 58b and 58e possessed DNA non-intercalation properties as seen with etoposide, serving as topo II poison. In conclusion, this study showed that 3-phenyl-9-aminoacridone derivatives are potential inhibitor of topo IIα/β both by catalytic inhibition and poison as non-intercalator of DNA.
{"title":"Synthesis, SAR, and in Silico ADME Screening Studies of Some 9-Amino-3-Phenylacridone Derivatives as Topoisomerase II Inhibitors","authors":"Abiodun S. Oyedele, Toluwase H. Fatoki, Esha Dalvie, Neil Osheroff, Cosmas O. Okoro","doi":"10.4236/ojmc.2023.132002","DOIUrl":"https://doi.org/10.4236/ojmc.2023.132002","url":null,"abstract":"Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize and computationally evaluate pharmacological potential of some derivatives of 9-amino-3-phenylacridone, as topoisomerase II (Topo II) inhibitors. In this study, 10 derivatives of 3-phenyl-9-aminoacridone were chemically synthesized and characterized, and the potential pharmacological indications of these compounds were computationally predicted by methods such as ADMET prediction, molecular target prediction and molecular docking. The results showed that two derivatives (58e and 58j) were non-permeant of blood-brain barrier, and this property was found similar to that of amsacrine and etoposide. The results of molecular docking of the ten derivatives of 3-phenyl-9-aminoacridone that were synthesized in this work showed that the synthetic compounds (58a-j) and the standard drugs have overall best binding affinities for human acetylcholine esterase than butyrylcholinesterase, and overall best binding affinities for human topo IIα than human topo IIβ. Overall, the results of this study suggest that the synthetic compounds 58a, 58c, 58f, 58g, and 58i could probably inhibit topo IIα by catalytic inhibition as seen with amsacrine, but only 58b and 58e possessed DNA non-intercalation properties as seen with etoposide, serving as topo II poison. In conclusion, this study showed that 3-phenyl-9-aminoacridone derivatives are potential inhibitor of topo IIα/β both by catalytic inhibition and poison as non-intercalator of DNA.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135360664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.4236/ojmc.2022.121001
E. Lisic, Sarah N. Grossarth, Sarah B. Bowman, Jessica L. Hill, Michael W. Beck, J. Deweese, Xiaohua Jiang
{"title":"New Copper (II), Palladium (II), and Platinum (II) 2-Acetylpyrazine Tert-Butylthiosemicarbazone Complexes: Inhibition of Human Topoisomerase IIα and Activity against Breast Cancer Cells","authors":"E. Lisic, Sarah N. Grossarth, Sarah B. Bowman, Jessica L. Hill, Michael W. Beck, J. Deweese, Xiaohua Jiang","doi":"10.4236/ojmc.2022.121001","DOIUrl":"https://doi.org/10.4236/ojmc.2022.121001","url":null,"abstract":"","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74623744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.4236/ojmc.2022.122002
Rubina Bibi, A. Sadiq, E. Mughal
{"title":"Synthesis, Biological Evaluation, and SAR Studies of Varyingly Substituted 4-Thioflavonols","authors":"Rubina Bibi, A. Sadiq, E. Mughal","doi":"10.4236/ojmc.2022.122002","DOIUrl":"https://doi.org/10.4236/ojmc.2022.122002","url":null,"abstract":"","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84463731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-30DOI: 10.4236/ojmc.2021.112002
Coulibaly Bamoro, Fante Bamba, Koffi Téki Dindet Steve-Evanes, A. Vallin, V. Chagnault
Due to the continuous emergence and rapid spread of drug-resistant strains of bacteria, there is an urgent need for the development of novel antimicrobials. Along this line, the synthesis and antibacterial activity of 4,5-diphenylimidazol-2-thiol derivatives 2a-g and 6a-e are reported. The structures of the synthesized compounds were confirmed by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HRMS). All compounds were screened in vitro for their antibacterial activity against Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria) and also against Staphyloccocus aureus and Enterococcus faecalis (Gram-positive bacteria). The results showed most of the synthesized compounds have no antibacterial activity. However compound 6d was two-fold potent than ciprofloxacin against Staphylococcus aureus with Minimum Inhibitory Concentration (MIC) of 4 μg/mL and 6c showed moderate biological activity against Staphylococcus aureus (16 μg/mL) and Enterococcus faecalis (16 μg/mL).
{"title":"Design, Synthesis and Antibacterial Activity Evaluation of 4,5-Diphenyl-1H-Imidazoles Derivatives","authors":"Coulibaly Bamoro, Fante Bamba, Koffi Téki Dindet Steve-Evanes, A. Vallin, V. Chagnault","doi":"10.4236/ojmc.2021.112002","DOIUrl":"https://doi.org/10.4236/ojmc.2021.112002","url":null,"abstract":"Due to the continuous emergence and rapid spread of drug-resistant strains of bacteria, there is an urgent need for the development of novel antimicrobials. Along this line, the synthesis and antibacterial activity of 4,5-diphenylimidazol-2-thiol derivatives 2a-g and 6a-e are reported. The structures of the synthesized compounds were confirmed by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HRMS). All compounds were screened in vitro for their antibacterial activity against Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria) and also against Staphyloccocus aureus and Enterococcus faecalis (Gram-positive bacteria). The results showed most of the synthesized compounds have no antibacterial activity. However compound 6d was two-fold potent than ciprofloxacin against Staphylococcus aureus with Minimum Inhibitory Concentration (MIC) of 4 μg/mL and 6c showed moderate biological activity against Staphylococcus aureus (16 μg/mL) and Enterococcus faecalis (16 μg/mL).","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75790641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.4236/ojmc.2021.114004
Aminata P. Nacoulma, M. Compaoré, N. R. Meda, L. Pottier, V. Megalizzi, I. Somé, M. Kiendrebeogo
Over the past years, natural products have been used as useful candidates for prevention and treatment of skin disorders such as skin darkening. In this current research, Daniellia oliveri which was a potential source of cosmeceut-ical agent was selected to investigate its active components. Daniellic acid isolated from the oleoresin was characterized by using data from 1 H-NMR, 13 C-NMR, HSQC, IR, and online chemo-informatic analysis. The daniellic acid antioxidant, anti-proliferative, and tyrosinase inhibition capabilities were evaluated. This compound possessed an anti-DPPH and iron (III) reducing effect compared to quercetin. It was able to inhibit 9 tumor cells with IC 50 going from 0.03 mM (U373) to 0.14 mM (Malme-3M). Interestingly daniellic acid inhibits tyrosinase activity with 1.20 mM as IC 50 . The tyrosinase inhibition mechanism was noncompetitive mixed-type with un-significant effect on cell melanogenesis. Daniellic acids induced a half-reduction of melanin production in B16F10 cell in IBMX stimulation (p < 0.05). The same observation was effective in Malme-3M melanin production with a significant daniellic acid action than kojic acid (p < 0.05) without reducing cell viabilities. This bioactive daniellic acid could explain the traditional uses of oleoresins from Daniellia oliveri for genitor-urinary tract diseases treatments, wound healing, and skin ailments in Burkina Faso.
在过去的几年里，天然产品已被用作预防和治疗皮肤疾病(如皮肤变黑)的有用候选者。本研究选取具有潜在药妆原料潜力的牛头草对其活性成分进行了研究。采用1h - nmr、13c - nmr、HSQC、IR和在线化学信息学分析等方法对从油树脂中分离得到的丹尼尔酸进行了表征。对丹尼尔酸的抗氧化、抗增殖和酪氨酸酶抑制能力进行了评价。与槲皮素相比，该化合物具有抗dpph和铁(III)还原作用。能抑制9个肿瘤细胞，ic50从0.03 mM (U373)到0.14 mM (Malme-3M)。有趣的是，丹尼尔酸抑制酪氨酸酶活性的ic50为1.20 mM。酪氨酸酶抑制机制为非竞争性混合型，对细胞黑色素生成影响不显著。Daniellic酸诱导IBMX刺激下B16F10细胞黑色素生成减少一半(p < 0.05)。同样的观察结果对Malme-3M黑色素的产生也有效，但丹尼尔酸的作用显著高于曲酸(p < 0.05)，且不降低细胞存活率。这种具有生物活性的丹尼尔酸可以解释在布基纳法索，从丹尼尔利亚提取的油树脂用于治疗生殖-泌尿系统疾病、伤口愈合和皮肤疾病的传统用途。
{"title":"Anti-Melanogenesis Effect of Daniellic Acid Isolated from Daniellia oliveri (Rolfe) Hutch. & Dalziel (Leguminosae) Oleoresin of Burkina Faso","authors":"Aminata P. Nacoulma, M. Compaoré, N. R. Meda, L. Pottier, V. Megalizzi, I. Somé, M. Kiendrebeogo","doi":"10.4236/ojmc.2021.114004","DOIUrl":"https://doi.org/10.4236/ojmc.2021.114004","url":null,"abstract":"Over the past years, natural products have been used as useful candidates for prevention and treatment of skin disorders such as skin darkening. In this current research, Daniellia oliveri which was a potential source of cosmeceut-ical agent was selected to investigate its active components. Daniellic acid isolated from the oleoresin was characterized by using data from 1 H-NMR, 13 C-NMR, HSQC, IR, and online chemo-informatic analysis. The daniellic acid antioxidant, anti-proliferative, and tyrosinase inhibition capabilities were evaluated. This compound possessed an anti-DPPH and iron (III) reducing effect compared to quercetin. It was able to inhibit 9 tumor cells with IC 50 going from 0.03 mM (U373) to 0.14 mM (Malme-3M). Interestingly daniellic acid inhibits tyrosinase activity with 1.20 mM as IC 50 . The tyrosinase inhibition mechanism was noncompetitive mixed-type with un-significant effect on cell melanogenesis. Daniellic acids induced a half-reduction of melanin production in B16F10 cell in IBMX stimulation (p < 0.05). The same observation was effective in Malme-3M melanin production with a significant daniellic acid action than kojic acid (p < 0.05) without reducing cell viabilities. This bioactive daniellic acid could explain the traditional uses of oleoresins from Daniellia oliveri for genitor-urinary tract diseases treatments, wound healing, and skin ailments in Burkina Faso.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85035492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.4236/ojmc.2021.113003
Achi Patrick-Armand, Coulibali Sioménan, Zon Doumadé, Timotou Adéyolé, B. Eric, Touré Daouda, Sissouma Drissa, A. Ané
{"title":"Synthesis and Antibacterial Activities of New 2-(Benzylthio)pyrimidines and 2-(Benzimidazolylmethylthio)pyrimidines Derivatives","authors":"Achi Patrick-Armand, Coulibali Sioménan, Zon Doumadé, Timotou Adéyolé, B. Eric, Touré Daouda, Sissouma Drissa, A. Ané","doi":"10.4236/ojmc.2021.113003","DOIUrl":"https://doi.org/10.4236/ojmc.2021.113003","url":null,"abstract":"","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79365824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-24DOI: 10.4236/ojmc.2020.102003
S. S. Neyadi, A. Adem, N. Amir, I. Abdou
The peroxisome proliferator activator receptor-γ (PPAR-γ) remained the most effective target for management of diabetes mellitus. The present work endeavors rational designing new PPAR-γ agonist bearing cyclotriphosphazene and thiazolidine-2,4-dione scaffolds. Thiazolidinedione (TZD) derivatives are the novel class of oral antidiabetic drugs which are selective agonist for the nuclear PPARγ that enhances the transcription of several insulin responsive genes but TZDs are known to cause weight gain, hepatotoxicity and fluid retention. So, cyclotriphosphazene containing thiazolidine-2,4-dione was designed, synthesized as PPARγ agonist. The in-vitro antidiabetic activity showed that compound 8 has similar activity and exhibited higher glucose uptake in comparison to pioglitazone as reference drugs. This research opened new avenues for smart designing of molecules with high efficiency towards the management of hyperglycemia.
{"title":"Targeting PPARγ Receptor Using New Phosphazene Derivative Containing Thiazolidinedione: Design, Synthesis, and Glucose Uptake","authors":"S. S. Neyadi, A. Adem, N. Amir, I. Abdou","doi":"10.4236/ojmc.2020.102003","DOIUrl":"https://doi.org/10.4236/ojmc.2020.102003","url":null,"abstract":"The peroxisome proliferator activator receptor-γ (PPAR-γ) remained the most effective target for management of diabetes mellitus. The present work endeavors rational designing new PPAR-γ agonist bearing cyclotriphosphazene and thiazolidine-2,4-dione scaffolds. Thiazolidinedione (TZD) derivatives are the novel class of oral antidiabetic drugs which are selective agonist for the nuclear PPARγ that enhances the transcription of several insulin responsive genes but TZDs are known to cause weight gain, hepatotoxicity and fluid retention. So, cyclotriphosphazene containing thiazolidine-2,4-dione was designed, synthesized as PPARγ agonist. The in-vitro antidiabetic activity showed that compound 8 has similar activity and exhibited higher glucose uptake in comparison to pioglitazone as reference drugs. This research opened new avenues for smart designing of molecules with high efficiency towards the management of hyperglycemia.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90246643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-24DOI: 10.4236/ojmc.2020.102004
Verma Deepshikha, P. Rajasekharan
With the help of the solid phase peptide synthesizing method, we synthesized Kalata B2 cyclotide and the final product was purified by preparative HPLC. The sequence of Kalata B2 is GLPVCGETCFGGTCNTPGCSCTWPICTRD and its m/z M + H mass is 2955.53. It had been first isolated from Oldenlandia affinis plant leaves extract which belongs to Rubiaceae family. The synthesis of Kalata B2 has been characterized through UPLC/MS, LC/MS, CD, 1HNMR, and IR.
采用固相多肽合成法合成了Kalata B2环肽，并用制备型高效液相色谱法对产物进行了纯化。Kalata B2序列为GLPVCGETCFGGTCNTPGCSCTWPICTRD, m/z m + H质量为2955.53。该化合物首次从茜草科植物亲和叶提取物中分离得到。通过UPLC/MS、LC/MS、CD、1HNMR和IR对Kalata B2的合成进行了表征。
{"title":"Synthesis and Characterization of Kalata B2 Cyclotide (GLPVCGETCFGGTCNTPGCSCTWPICTRD) on Wang Resin, as Solid Support","authors":"Verma Deepshikha, P. Rajasekharan","doi":"10.4236/ojmc.2020.102004","DOIUrl":"https://doi.org/10.4236/ojmc.2020.102004","url":null,"abstract":"With the help of the solid phase peptide synthesizing method, we synthesized Kalata B2 cyclotide and the final product was purified by preparative HPLC. The sequence of Kalata B2 is GLPVCGETCFGGTCNTPGCSCTWPICTRD and its m/z M + H mass is 2955.53. It had been first isolated from Oldenlandia affinis plant leaves extract which belongs to Rubiaceae family. The synthesis of Kalata B2 has been characterized through UPLC/MS, LC/MS, CD, 1HNMR, and IR.","PeriodicalId":68630,"journal":{"name":"药物化学期刊(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89164284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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