Article
Chemistry, Organic
Lizeth Bodero, Sara Parente, Federico Arrigoni, Annika Klimpel, Ines Neundorf, Silvia Gazzola, Umberto Piarulli
Summary: Two new Drug Delivery Systems (DDS) containing the cyclo[DKP-isoDGR] integrin ligand and the cytotoxic agent Paclitaxel (PTX) were synthesized to investigate their influences on cellular uptake and cytotoxicity. Compound 3 showed significantly higher potency compared to compound 2, with reduced potency loss in comparison to PTX.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kerong Guo, Jian Li, Yingdong Jia, Xiaojuan Yang, Xiqing Yan, Liqiang Wu
Summary: In this study, novel quinolinedione-linked sulfonylpiperazine derivatives were investigated as NQO1-directed antitumor agents. Most of the compounds showed higher effectiveness in inhibiting cancer cell proliferation compared to 5-Fu and TSA. Among them, compound 22r exhibited significant anti-proliferative activity against NQO1-rich cancer cells and was recognized as an excellent substrate for NQO1. Mechanistic studies revealed that 22r induced ROS production, DNA damage, and apoptosis in HepG2 cells. Remarkably, compound 22r also showed excellent anticancer activity in HepG2 xenograft models. Overall, this study demonstrated that compound 22r could be a promising strategy for the treatment of malignant tumors.
BIOORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Fateme Azimi, Homa Azizian, Mohammad Najafi, Ghadamali Khodarahmi, Lotfollah Saghaei, Motahareh Hassanzadeh, Jahan B. Ghasemi, Mohammad Ali Faramarzi, Bagher Larijani, Farshid Hassanzadeh, Mohammad Mahdavi
Summary: New derivatives of biphenyl pyrazole-benzofuran hybrids were synthesized and evaluated for their inhibitory effect against alpha-glucosidase activity in vitro. The most active compound 8e was identified as a competitive inhibitor of alpha-glucosidase. Molecular docking and dynamic simulations revealed the interaction modes of the compounds with the enzyme's active site.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Chong Zhang, Limin Yang, Xiaojuan Yang, Qinghe Gao, Yan Qu, Liqiang Wu
Summary: The current study developed various novel napabucasin-melatonin hybrids as potent STAT3 inhibitors. Multiple biological studies have shown that many compounds have strong inhibition against different tumor cells. Among them, compound 7e demonstrated enhanced inhibition against HepG2, MDA-MB-231, and A549 cells compared to napabucasin, with IC50 values of 1.06, 1.38, and 1.3 μM, respectively. The compound was found to bind to the SH2 domain in STAT3, inhibiting its activation and downstream gene expression, and inducing cancer cell apoptosis in a concentration-dependent manner. Moreover, in vivo experiments demonstrated that 20 mg/kg (i.p.) of compound 7e effectively suppressed the development of HepG2 xenografts in mice without causing weight loss, suggesting its potential as an antitumor agent.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Kai-Yan Xu, Xue-Ting Wang, Lei Cheng, Qi-Hang Cui, Jian-Tao Shi, Li-Wen Zhang, Shi-Wu Chen
Summary: A series of quinoxalinone derivatives were designed and synthesized as BRD4 inhibitors, among which compound X9 showed potent activity against BRD4 and HepG2 cell proliferation with less toxicity. Furthermore, compound X9 could inhibit colony formation and migration of HepG2 cells, induce apoptosis, and arrest cell cycle progression. In conclusion, quinoxalinone derivatives are potential core structures as BRD4 inhibitors, and compound X9 may be effective for liver cancer therapy.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yang Zhou, Jiao Zou, Xi Zhong, Jing Xu, Kun Gou, Xia Zhou, Yue Zhou, Xinyu Yang, Xinqi Guan, Yu Zhang, Donglin Chen, Xiaobo Cen, Youfu Luo, Yinglan Zhao
Summary: A series of novel pyrazole amides were designed and optimized as potential inhibitors of mitochondrial complex I. Among them, SCAL-255 and SCAL-266 showed good safety and significant inhibitory activity against cancer cells, suggesting their potential as promising CI inhibitors for treating OXPHOS-dependent cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nayera I. Mansour, Selwan M. El-Sayed, Nadia S. El-Gohary, Naglaa I. Abdel-Aziz, Hussein I. El-Subbagh, Mariam A. Ghaly
Summary: A series of novel phthalimide derivatives were synthesized and evaluated for their in vitro antitumor activity. Compound 32 showed the most potent activity, while compounds 33, 22, and 24 exhibited strong activity against all tested cell lines. Compound 32 also displayed promising EGFR-TK inhibition activity, making it a potential template for further optimization.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Li-Qiang Wu, Xin Ma, Zhao-Peng Liu
Summary: A series of novel NQO1-targeted anticancer agents were synthesized, with compound 5k identified as a favorable NQO1 substrate that significantly suppressed tumor growth and decreased mitochondrial membrane potential in tumor cells.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Sophia D. Staerz, Corey L. Jones, Jetze J. Tepe
Summary: Neurodegenerative diseases are characterized by the oligomerization and aggregation of specific intrinsically disordered proteins, and enhancing 20S proteasome-mediated proteolysis could be a promising therapeutic approach.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Gang Li, Jia-Qiang Wu, Xiaojia Cai, Wen Guan, Zhijun Zeng, Yanghui Ou, Xiaoyun Wu, Jiayu Li, Xiangxiang Fang, Jinling Liu, Yali Zhang, Huamin Wang, Canqiang Yin, Hongliang Yao
Summary: A series of diaryl heterocyclic analogues were synthesized as tubulin polymerization inhibitors. Compound 6y exhibited the highest antiproliferative activity against HCT-116 colon cancer cells and effectively inhibited tubulin polymerization in vitro. It also showed high metabolic stability on human liver microsomes and suppressed tumor growth in a HCT-116 mouse colon model without toxicity. These results suggest that 6y represents a new class of tubulin inhibitors worthy of further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mingcheng Qian, Xinyu Jiang, Mingting Zhang, Lijuan Hu, Huimin Liu, Shuai Zhao, Xiaoying Zhou, Xin Chen
Summary: In this study, two series of modified matrine analogs were synthesized, with analog B11 showing the best antiproliferative activity in vitro and inducing G1 phase cell cycle arrest and dose-dependent cell apoptosis in A549 cells. Molecular modeling indicated that B11 had a higher docking score compared to its precursor and the parent compound, suggesting it as a potential lead compound for further anticancer research.
CHEMISTRY & BIODIVERSITY
(2021)
Article
Chemistry, Medicinal
Hui Shen, Yiran Ge, Junwei Wang, Hui Li, Yungen Xu, Qihua Zhu
Summary: Two series of novel compounds with PARP-1 inhibition activity were designed and synthesized, among which compound II-4 showed high PARP-1 inhibition activity and anti-proliferative activity, indicating its potential as a lead compound for the development of PARP-1 inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Deblina Roy, Mohammad Anas, Ashan Manhas, Satyen Saha, Niti Kumar, Gautam Panda
Summary: In this study, a series of quinoline-imidazole hybrid compounds were synthesized and evaluated for their blood-stage antimalarial activity against Plasmodium falciparum. The results showed that one of the compounds exhibited significant antimalarial efficacy with low cytotoxicity and high selectivity. Furthermore, the study revealed the influence of substituents on the quinoline ring and the role of stereochemistry in the inhibitory activity.
BIOORGANIC CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Paola Oliva, Romeo Romagnoli, Barbara Cacciari, Stefano Manfredini, Chiara Padroni, Andrea Brancale, Salvatore Ferla, Ernest Hamel, Diana Corallo, Sanja Aveic, Noemi Milan, Elena Mariotto, Giampietro Viola, Roberta Bortolozzi
Summary: In this study, two series of compounds were found to exhibit moderate to potent antiproliferative activity against cancer cells. The interaction with tubulin led to cell apoptosis and inhibition of cell growth.
Article
Chemistry, Medicinal
Dandan Xu, Deqiao Sun, Wei Wang, Xia Peng, Zhengsheng Zhan, Yinchun Ji, Yanyan Shen, Meiyu Geng, Jing Ai, Wenhu Duan
Summary: Axl has become an attractive target for cancer therapy due to its correlation with tumor growth, metastasis, poor survival, and drug resistance. Compound 13b, among the new Axl inhibitors studied, showed high enzymatic and cellular potencies and promising therapeutic effects in animal models, indicating its potential as a lead compound for new antitumor drug discovery.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)