Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro
In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 μM) and low cytotoxicity (>800 μM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound...
Source: Bioorganic Chemistry - March 31, 2024 Category: Chemistry Authors: Kai Sun Zhongmou Zhang Jiani Xing Shouye Ma Yongzhuang Ge Lu Xia Xiaoqiong Diao Yonghong Li Zhanyong Wei Zhenya Wang Source Type: research
Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study
Bioorg Chem. 2024 Mar 26;146:107292. doi: 10.1016/j.bioorg.2024.107292. Online ahead of print.ABSTRACTBreast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthes...
Source: Bioorganic Chemistry - March 31, 2024 Category: Chemistry Authors: Eman Mansour Ahmed A Abd-Rabou Mohamed A El-Atawy Hoda A Ahmed Ahmed F El-Farargy Heba K Abd El-Mawgoud Source Type: research
Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro
In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 μM) and low cytotoxicity (>800 μM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound...
Source: Bioorganic Chemistry - March 31, 2024 Category: Chemistry Authors: Kai Sun Zhongmou Zhang Jiani Xing Shouye Ma Yongzhuang Ge Lu Xia Xiaoqiong Diao Yonghong Li Zhanyong Wei Zhenya Wang Source Type: research
Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study
Bioorg Chem. 2024 Mar 26;146:107292. doi: 10.1016/j.bioorg.2024.107292. Online ahead of print.ABSTRACTBreast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthes...
Source: Bioorganic Chemistry - March 31, 2024 Category: Chemistry Authors: Eman Mansour Ahmed A Abd-Rabou Mohamed A El-Atawy Hoda A Ahmed Ahmed F El-Farargy Heba K Abd El-Mawgoud Source Type: research
Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro
In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 μM) and low cytotoxicity (>800 μM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound...
Source: Bioorganic Chemistry - March 31, 2024 Category: Chemistry Authors: Kai Sun Zhongmou Zhang Jiani Xing Shouye Ma Yongzhuang Ge Lu Xia Xiaoqiong Diao Yonghong Li Zhanyong Wei Zhenya Wang Source Type: research
Induction of breast cancer cell apoptosis by novel thiouracil-fused heterocyclic compounds through boosting of Bax/Bcl-2 ratio and DFT study
Bioorg Chem. 2024 Mar 26;146:107292. doi: 10.1016/j.bioorg.2024.107292. Online ahead of print.ABSTRACTBreast cancer is a common public health disease causing mortality worldwide. Thus, providing novel chemotherapies that tackle breast cancer is of great interest. In this investigation, novel pyrido[2,3-d]pyrimidine derivatives 3,4,(6a-c),(8a,b),9-20 were synthesized and characterized using a variety of spectrum analyses. The geometric and thermal parameters of the novel thiouracil derivatives 3,4,6a,(8a,b),11,12,17,18, 19 were measured using density functional theory (DFT) via DFT/B3LYP/6-31 + G(d,p) basis set. All synthes...
Source: Bioorganic Chemistry - March 31, 2024 Category: Chemistry Authors: Eman Mansour Ahmed A Abd-Rabou Mohamed A El-Atawy Hoda A Ahmed Ahmed F El-Farargy Heba K Abd El-Mawgoud Source Type: research
The new N < sup > 2 < /sup > , N < sup > 4 < /sup > -diphenylpyridine-2,4-diamine deuterated derivatives as EGFR inhibitors to overcome C797S-mediated resistance
Bioorg Chem. 2024 Mar 26;146:107313. doi: 10.1016/j.bioorg.2024.107313. Online ahead of print.ABSTRACTA series of new deuterated and non-deuterated N2, N4-diphenylpyridine - 2,4-diamine derivatives were synthesized and evaluated as EGFR C797S-mediated resistance inhibitors. Most of these compounds exhibited potent antiproliferative activity against Baf3-EGFR L858R/T790M/C797S and Baf3-EGFR Del19/T790M/C797S cancel cell lines, with IC50 values in the nanomolar concentration range. Among them, compound 14l represented the most active compound with IC50 values of 8-11 nM. Interestingly, metabolic stability assay with rat live...
Source: Bioorganic Chemistry - March 30, 2024 Category: Chemistry Authors: Jiadai Liu Wenyan Nie Haoran Nie Han Yao Yuanyuan Ren Longcai Cao Jiaqi Qiu Mengxuan Wang Xingshu Li Baijiao An Xian Jia Source Type: research
The new N < sup > 2 < /sup > , N < sup > 4 < /sup > -diphenylpyridine-2,4-diamine deuterated derivatives as EGFR inhibitors to overcome C797S-mediated resistance
Bioorg Chem. 2024 Mar 26;146:107313. doi: 10.1016/j.bioorg.2024.107313. Online ahead of print.ABSTRACTA series of new deuterated and non-deuterated N2, N4-diphenylpyridine - 2,4-diamine derivatives were synthesized and evaluated as EGFR C797S-mediated resistance inhibitors. Most of these compounds exhibited potent antiproliferative activity against Baf3-EGFR L858R/T790M/C797S and Baf3-EGFR Del19/T790M/C797S cancel cell lines, with IC50 values in the nanomolar concentration range. Among them, compound 14l represented the most active compound with IC50 values of 8-11 nM. Interestingly, metabolic stability assay with rat live...
Source: Bioorganic Chemistry - March 30, 2024 Category: Chemistry Authors: Jiadai Liu Wenyan Nie Haoran Nie Han Yao Yuanyuan Ren Longcai Cao Jiaqi Qiu Mengxuan Wang Xingshu Li Baijiao An Xian Jia Source Type: research
Structure-activity relationship and biofilm formation-related gene targets of oleanolic acid-type saponins from Pulsatilla chinensis against Candida albicans
Bioorg Chem. 2024 Mar 25;146:107311. doi: 10.1016/j.bioorg.2024.107311. Online ahead of print.ABSTRACTIn the course of our investigations of antifungal natural products, the structure-activity relationship and antifungal activities of oleanolic acid-type saponins (1-28) from Pulsatilla chinensis against human and plant pathogenic fungi were elucidated. The analysis of structure-activity relationship of oleanolic acid-type saponins showed that the free carboxyl at C-28 was essential for their antifungal activities; the free hydroxyl group at the C-23 site of oleanolic acid-type saponins played a crucial role in their antifu...
Source: Bioorganic Chemistry - March 28, 2024 Category: Chemistry Authors: Junfeng Tan Zengguang Zhang Dan Zheng Yu Mu Bixuan Cao Junwei Yang Li Han Xueshi Huang Source Type: research
Discovery of macrocyclic CDK2/4/6 inhibitors with improved potency and DMPK properties through a highly efficient macrocyclic drug design platform
Bioorg Chem. 2024 Mar 15;146:107285. doi: 10.1016/j.bioorg.2024.107285. Online ahead of print.ABSTRACTCyclin-dependent kinases (CDKs) are critical cell cycle regulators that are often overexpressed in tumors, making them promising targets for anti-cancer therapies. Despite substantial advancements in optimizing the selectivity and drug-like properties of CDK inhibitors, safety of multi-target inhibitors remains a significant challenge. Macrocyclization is a promising drug discovery strategy to improve the pharmacological properties of existing compounds. Here we report the development of a macrocyclization platform that en...
Source: Bioorganic Chemistry - March 28, 2024 Category: Chemistry Authors: Fanye Meng Jinxin Liu Zhongying Cao Jiaojiao Yu Barbara Steurer Yilin Yang Yazhou Wang Xin Cai Man Zhang Feng Ren Alex Aliper Xiao Ding Alex Zhavoronkov Source Type: research
Design, synthesis and biological evaluation of new 2,6-difluorinated phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates as new antimicrotubule agents
In this study, we evaluated the effect of the difluorination of the aromatic ring bearing the imidazolidin-2-one moiety (ring A) at positions 3, 5 and 2, 6 on their antiproliferative activity on four cancer cell lines, their ability to disrupt the microtubules and their toxicity toward chick embryos. We thus synthesized, characterized and biologically evaluated 24 new difluorinated PIB-SO derivatives designated as phenyl 3,5-difluoro-4-(2-oxoimidazolidin-1-yl)benzenesulfonates (3,5-PFB-SOs, 4-15) and phenyl 2,6-difluoro-4-(2-oxoimidazolidin-1-yl)benzenesulfonates (2,6-PFB-SOs, 16-27). The concentration of the drug required...
Source: Bioorganic Chemistry - March 28, 2024 Category: Chemistry Authors: Chahrazed Bouzriba Mathieu Gagn é-Boulet Atziri Corin Chavez Alvarez Vincent Ouellette Isabelle Laverdi ère S ébastien Fortin Source Type: research
Structure-activity relationship and biofilm formation-related gene targets of oleanolic acid-type saponins from Pulsatilla chinensis against Candida albicans
Bioorg Chem. 2024 Mar 25;146:107311. doi: 10.1016/j.bioorg.2024.107311. Online ahead of print.ABSTRACTIn the course of our investigations of antifungal natural products, the structure-activity relationship and antifungal activities of oleanolic acid-type saponins (1-28) from Pulsatilla chinensis against human and plant pathogenic fungi were elucidated. The analysis of structure-activity relationship of oleanolic acid-type saponins showed that the free carboxyl at C-28 was essential for their antifungal activities; the free hydroxyl group at the C-23 site of oleanolic acid-type saponins played a crucial role in their antifu...
Source: Bioorganic Chemistry - March 28, 2024 Category: Chemistry Authors: Junfeng Tan Zengguang Zhang Dan Zheng Yu Mu Bixuan Cao Junwei Yang Li Han Xueshi Huang Source Type: research
Discovery of macrocyclic CDK2/4/6 inhibitors with improved potency and DMPK properties through a highly efficient macrocyclic drug design platform
Bioorg Chem. 2024 Mar 15;146:107285. doi: 10.1016/j.bioorg.2024.107285. Online ahead of print.ABSTRACTCyclin-dependent kinases (CDKs) are critical cell cycle regulators that are often overexpressed in tumors, making them promising targets for anti-cancer therapies. Despite substantial advancements in optimizing the selectivity and drug-like properties of CDK inhibitors, safety of multi-target inhibitors remains a significant challenge. Macrocyclization is a promising drug discovery strategy to improve the pharmacological properties of existing compounds. Here we report the development of a macrocyclization platform that en...
Source: Bioorganic Chemistry - March 28, 2024 Category: Chemistry Authors: Fanye Meng Jinxin Liu Zhongying Cao Jiaojiao Yu Barbara Steurer Yilin Yang Yazhou Wang Xin Cai Man Zhang Feng Ren Alex Aliper Xiao Ding Alex Zhavoronkov Source Type: research
Design, synthesis and biological evaluation of new 2,6-difluorinated phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates as new antimicrotubule agents
In this study, we evaluated the effect of the difluorination of the aromatic ring bearing the imidazolidin-2-one moiety (ring A) at positions 3, 5 and 2, 6 on their antiproliferative activity on four cancer cell lines, their ability to disrupt the microtubules and their toxicity toward chick embryos. We thus synthesized, characterized and biologically evaluated 24 new difluorinated PIB-SO derivatives designated as phenyl 3,5-difluoro-4-(2-oxoimidazolidin-1-yl)benzenesulfonates (3,5-PFB-SOs, 4-15) and phenyl 2,6-difluoro-4-(2-oxoimidazolidin-1-yl)benzenesulfonates (2,6-PFB-SOs, 16-27). The concentration of the drug required...
Source: Bioorganic Chemistry - March 28, 2024 Category: Chemistry Authors: Chahrazed Bouzriba Mathieu Gagn é-Boulet Atziri Corin Chavez Alvarez Vincent Ouellette Isabelle Laverdi ère S ébastien Fortin Source Type: research
Synthesis of narrow-spectrum anti-mycobacterial molecules without effect on the diversity of gut microbiota in mice based on the structure of rifampicin
Bioorg Chem. 2024 Mar 13;146:107282. doi: 10.1016/j.bioorg.2024.107282. Online ahead of print.ABSTRACTRifampicin (RIF) is a broad-spectrum antimicrobial agent that is also a first-line drug for treating tuberculosis (TB). Based on the naphthyl ring structure of RIF this study synthesized 16 narrow-spectrum antimicrobial molecules that were specifically anti-Mycobacterium tuberculosis (Mtb). The most potent candidate was 2-((6-hydroxynaphthalen-2-yl) methylene) hydrazine-1-carbothioamide (compound 3c) with minimum inhibitory concentration (MIC) of 1 μg/mL against Mtb. Synergistic anti-Mtb test indicated that none of the co...
Source: Bioorganic Chemistry - March 27, 2024 Category: Chemistry Authors: Jun-Xian Chen Hong-Mei Dong Yu-Xiang Cai Li-Xia Tian Zai-Chang Yang Source Type: research
