Article
Chemistry, Medicinal
Heping Zhu, Shilong Ying, Bingluo Zhou, Xiao Liang, Quan He, Ping Song, Xinyang Hu, Keqiang Shi, Mingteng Xiong, Hongchuan Jin, Yuanjiang Pan
Summary: A series of novel 2-aryl-3-sulfonamido-pyridines (HoAns) compounds were designed, synthesized, and evaluated for their antiproliferative activities, with HoAn32 demonstrating the most potent activity and microtubule-targeting effect in cancer cell lines. Mechanism studies showed that HoAn32 bound to the colchicine site of b-tubulin, resulting in multiple anti-cancer effects.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Godshelp O. Egharevba, Ahmed Kamal, Omotayo O. Dosumu, Sunitha Routhu, Olatomide A. Fadare, Stephen O. Oguntoye, Stanislaus N. Njinga, Abimbola P. Oluyori
Summary: The novel 1,1-diaryl vinyl-sulfones analogues were synthesized and screened for their antiproliferative activity against various cancer cell lines. The compounds showed better cytotoxicity against certain cancer cell lines and had no toxicity towards normal cells. Compounds with higher cell permeability demonstrated optimal cytotoxicity, highlighting the importance of cell permeability in enhancing the cytotoxicity of these compounds.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Alexander Scherbakov, Alexey V. Zakharov, Ekaterina I. Mikhaevich, Diana I. Salnikova, Anton V. Yadykov, Arina A. Kozhevnikova, Valerii Z. Shirinian
Summary: This study investigated the photochemical properties and antiproliferative activity of furanone analogues of combretastatin A-4, revealing that the introduction of an arylidene moiety significantly improved photostability and that antiproliferative activity depends on the nature of the aryl residue in the arylidene moiety.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Dalal Sulaiman Alshaya, Rana M. O. Tawakul, Islam Zaki, Ali H. Abu Almaaty, Eman Fayad, Yasmin M. Abd El-Aziz
Summary: A new series of acrylic acid and acrylate ester derivatives were synthesized and evaluated for their antiproliferative activity against MCF-7 breast carcinoma cells. Methyl acrylate ester 6e showed the highest cytotoxicity with an IC50 value of 2.57 +/- 0.16 mu M and exhibited inhibition of beta-tubulin polymerization. Compound 6e arrested MCF-7 cells at the G2/M phase and enhanced apoptotic power, while also affecting the gene expression levels of p53, Bax, and Bcl-2.
Article
Biochemistry & Molecular Biology
Ashish Ranjan Dwivedi, Suraj Singh Rawat, Vijay Kumar, Naveen Kumar, Piyush Anand, Ravi Prakash Yadav, Somesh Baranwal, Amit Prasad, Vinod Kumar
Summary: In this study, 16 novel compounds were synthesized and evaluated for their anticancer activity. It was found that two of the compounds exhibited inhibitory effects on cancer cell proliferation and induced mitochondria-mediated apoptosis. Additionally, one of the compounds showed significant tubulin polymerization inhibition activity. Computational studies revealed that this compound had good binding affinities in the colchicine domain and thermodynamic stability. Therefore, these compounds have the potential to be developed as potent anticancer agents.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jung-Seop Lee, In-ho Song, Shrikant Dashrath Warkad, Gyu Seong Yeom, Pramod B. Shinde, Keum-soo Song, Satish Balasaheb Nimse
Summary: In this study, a series of 2,5-substituted-1H-benzo[d]imidazole derivatives were synthesized and it was demonstrated that compounds B15, B16, B19, and B20 exhibit excellent anticancer activity.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Dong-Jun Fu, Ting Wang
Summary: In this study, a series of potential dual tubulin-NEDDylation inhibitors were synthesized and evaluated. Compound C11 exhibited the strongest antiproliferative activity and showed potent inhibition against tubulin and NEDDylation.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sonal Jaiswal, Sushanta K. Parida, Sandip Murarka, Priyanka Singh
Summary: The study identifies S-aryl dithiocarbamates as a potential class of anticancer drugs, which inhibit cancer cell proliferation, induce apoptosis, and exhibit microtubule-stabilizing properties.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ibrahim H. Eissa, Mohammed A. Dahab, Mohamed K. Ibrahim, Nawaf A. Alsaif, A. Z. Alanazi, Sally Eissa, Ahmed B. M. Mehany, Andre M. Beauchemin
Summary: Thirty-five new colchicine binding site inhibitors were designed and synthesized based on the 1,2,4-triazin3(2H)-one nucleus. Two compounds showed significant antiproliferative effects against three human cancer cell lines, and further investigation revealed their potential as tubulin polymerization inhibitors. The synthesized compounds demonstrated selectivity against cancer cells and upregulated levels of active caspase-3 and pro-apoptotic protein Bax, suggesting their potential as anti-cancer agents. Additionally, in silico studies showed promising interactions with the colchicine binding site and favorable pharmacokinetic properties.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Cong-Min Peng, Shih-Wei Wang, Yi-Lin Hwang, Wen-Chun Sun, Li-Pin Chiu, Yi-Ting Liu, Yu-Wei Lai, Hsueh-Yun Lee
Summary: The in situ CuI-mediated cyclization methodology was used to synthesize benzimidazoles with different substitution manner. Structure-activity relationship (SAR) study confirmed the significance of the 5,6,7-trimethoxybenzimidazole moiety. Representative derivatives exhibited potent antiproliferative activity against A549, HCT-116, and PC-3 cells, as well as inhibition of tubulin polymerization. Compound 10 showed the most promising activity with an IC50 value of 0.07 μM against cancer cell growth and 0.26 μM against tubulin polymerization.
Article
Chemistry, Medicinal
Romeo Romagnoli, Paola Oliva, Maria Kimatrai Salvador, Stefano Manfredini, Chiara Padroni, Andrea Brancale, Salvatore Ferla, Ernest Hamel, Roberto Ronca, Federica Maccarinelli, Fatlum Rruga, Elena Mariotto, Giampietro Viola, Roberta Bortolozzi
Summary: Three different series of cis-restricted analogues of combretastatin A-4 (CA-4) were synthesized and evaluated for their antiproliferative activity against human cancer cell lines. Compound 11j showed superior intracellular target inhibition, blocking the cell cycle and inducing apoptosis via the mitochondrial pathway at low toxicity for normal cells. In vivo, compound 11j demonstrated significantly reduced tumor growth, even at lower doses, compared to CA-4P.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Xinjin Liu, Jinsen Liang, Yongshi Yu, Xin Han, Lei Yu, Feifei Chen, Zhichao Xu, Qi Chen, Mengyu Jin, Chune Dong, Hai-Bing Zhou, Ke Lan, Shuwen Wu
Summary: Influenza A viruses have a high antigenic shift and there are limited approved anti-influenza drugs available. Therefore, developing novel anti-influenza drugs is crucial for clinical treatment and prevention of influenza outbreaks. This study reports a series of novel aryl benzoyl hydrazide analogs that exhibit potent inhibitory activity against influenza A viruses. Compound 11q shows strong inhibitory activity against avian H5N1 flu strain, H1N1 virus, and Flu B virus, and possesses good oral bioavailability and inhibitory activity against influenza A virus in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Stefano Zoroddu, Paola Corona, Luca Sanna, Federica Borghi, Valentina Bordoni, Battistina Asproni, Gerard A. Pinna, Luigi Bagella, Gabriele Murineddu
Summary: A library of novel 1,3,4-oxadiazole bioisosteres was synthesized and evaluated for their cytotoxic activity. Several of the new compounds showed potent anticancer activity, surpassing the previously synthesized oxadiazole compound. The nature of the selenadiazole and thiadiazole rings may play a crucial role in the antitumor activity. These compounds exhibited strong cytotoxic effects in tumor cells compared to human primary cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Sahar S. Alghamdi, Rasha S. Suliman, Khlood Almutairi, Khawla Kahtani, Dimah Aljatli
Summary: Imidazole-containing compounds have shown promising therapeutic values in various disease conditions, including anti-cancer, anti-microbial, and anti-inflammatory activities. The electronic-rich characteristics of imidazole core scaffold enable it to readily bind with enzymes, proteins, and receptors, leading to potential mechanisms such as inhibition of COX-2 enzyme and protein kinase.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Andrea Spallarossa, Matteo Lusardi, Chiara Caneva, Aldo Profumo, Camillo Rosano, Marco Ponassi
Summary: A novel series of pyrimido-pyrimidine analogues have been synthesized with potent antiproliferative activity, although they show differences in binding to topoisomerase II alpha. The activity of the new compounds is influenced by the nature of the basic side chain and the substituents on the pyrimido-pyrimidine moiety.
Article
Chemistry, Medicinal
Zhongzhi Wu, Lubing Gu, Sicheng Zhang, Tao Liu, Pradeep B. Lukka, Bernd Meibohm, John C. Bollinger, Muxiang Zhou, Wei Li
Summary: The study reports a structurally optimized dual MDM2/XIAP inhibitor, leading to the discovery of a more potent analogue against EU-1, which exerts dual targeting effects and can induce cell death. The results suggest that the scaffold based on 14 shows promise for further development as a potential therapeutic agent for leukemia and other cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Monica L. Brown Lobbins, Imara-Safi O. Scott, Andrzej T. Slominski, Karen A. Hasty, Sicheng Zhang, Duane D. Miller, Wei Li, Tae-Kang Kim, Zorica Janjetovic, Tejesh S. Patel, Linda K. Myers, Arnold E. Postlethwaite
Summary: The study shows that the noncalcemic vitamin D analog, 17,20S(OH)(2)pD, can suppress total collagen production, dermal thickness, and total collagen content in a fibrosis model, while also increasing MMP-13 expression and decreasing expression of other related factors, as well as suppressing certain cytokines in the serum. This antifibrotic property offers new therapeutic approaches for fibrotic disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Wen Shuai, Guan Wang, Yiwen Zhang, Faqian Bu, Sicheng Zhang, Duane D. Miller, Wei Li, Liang Ouyang, Yuxi Wang
Summary: Microtubules are crucial in cellular functions and important targets for cancer therapy, but drug resistance and toxicity limit their efficacy. Dual-target drugs, combining tubulin with other anti-tumor agents, are considered promising to overcome limitations and improve therapeutic efficacy. Rational target combinations and design strategies of dual-target tubulin inhibitors are discussed for future directions.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hanxuan Li, Mohamed Moustafa Ibrahim, Hao Chen, Wei Li, Monica M. Jablonski
Summary: Glaucoma is a leading cause of permanent vision loss and current drugs are ineffective in halting the progression of the disease. Research has identified CACNA2D1 as a novel modulator of intraocular pressure (IOP) and validated the IOP-lowering effects of PRG and other compounds, providing potential new drug targets for treating glaucoma.
Article
Chemistry, Medicinal
Najah Albadari, Shanshan Deng, Hao Chen, Guannan Zhao, Junming Yue, Sicheng Zhang, Duane D. Miller, Zhongzhi Wu, Wei Li
Summary: The study describes the design and synthesis of a series of novel selective survivin inhibitors based on the hydroxyquinoline scaffold. The best compound identified, 12b, demonstrated potential anticancer activity by selectively targeting survivin and inducing cancer cell apoptosis. In vivo experiments showed that 12b effectively inhibited tumor growth and metastasis in melanoma and ovarian cancer models, suggesting promise for further preclinical development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Monica L. Brown Lobbins, Andrzej T. Slominski, Karen A. Hasty, Sicheng Zhang, Duane D. Miller, Wei Li, Tae-Kang Kim, Zorica Janjetovic, Robert C. Tuckey, Imara-Safi O. Scott, Linda K. Myers, Arnold E. Postlethwaite
Summary: This study demonstrates that 17,20S(OH)(2)pD can suppress type I collagen synthesis and decrease the expression of fibrosis-related mediators, offering a potential noncalcemic secosteroidal therapeutic approach for treating systemic sclerosis and fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Rajib Bhuniya, Xinrui Yuan, Longchuan Bai, Kathryn L. Howie, Rui Wang, Wei Li, Frank Park, Chao-Yie Yang
Summary: CDC20 overexpression is associated with poor prognosis in breast and other cancers. By designing new CDC20 inhibitors and improving their chemical structure, the antitumor activity can be enhanced. The most effective inhibitor, 22, shows promise for further development.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Cell & Tissue Engineering
W. Dong, B. C. Postlethwaite, P. A. Wheller, D. Brand, Y. Jiao, W. Li, L. K. Myers, W. Gu
Summary: This study found that supplementing with beta-caryophyllene (BCP) can increase the serum levels of klotho in mice, leading to improved bone properties and mineralization.
BONE & JOINT RESEARCH
(2022)
Article
Oncology
Raisa Krutilina, Kelli L. Hartman, Damilola Oluwalana, Hilaire C. Playa, Deanna N. Parke, Hao Chen, Duane D. Miller, Wei Li, Tiffany N. Seagroves
Summary: The study demonstrates the effectiveness of sabizabulin in inhibiting the growth and migration of HER2+ breast cancer cells, and inducing cell death. Sabizabulin is a promising alternative to taxanes for the treatment of HER2+ breast cancer, with similar anti-metastatic efficacy but better oral bioavailability and lower toxicity.
Review
Biochemistry & Molecular Biology
Najah Albadari, Wei Li
Summary: Survivin, a member of IAPs family, acts as a suppressor of apoptosis and is considered as an important cancer drug target due to its high expression in many types of human cancers. It is also involved in tumor cell resistance to chemotherapy and radiation. Downregulation of survivin can reduce tumor growth, induce apoptosis, and enhance tumor cell sensitivity to radiation and chemotherapy in different human tumor models.
Article
Chemistry, Medicinal
Satyanarayana Pochampally, Kelli L. Hartman, Rui Wang, Jiaxing Wang, Mi-Kyung Yun, Keyur Parmar, Hyunseo Park, Bernd Meibohm, Stephen W. White, Wei Li, Duane D. Miller
Summary: A new compound that inhibits cancer cell proliferation has been discovered and shows high anticancer activity and a long half-life. It exhibits significant potency against a wide range of cancer cell lines and has the potential for further preclinical evaluation as a candidate for development.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Najah Albadari, Yang Xie, Tao Liu, Rui Wang, Lubing Gu, Muxiang Zhou, Zhongzhi Wu, Wei Li
Summary: This study designed and synthesized a series of dual MDM2/XIAP inhibitors based on the tetrahydroquinoline scaffold and tested their cytotoxicity in human cancer cell lines. The compound 3e showed the best performance and effectively inhibited tumor growth in a 22Rv1 prostate cancer xenograft model. Overall, the results suggest that the tetrahydroquinoline scaffold has the potential for further preclinical development as a dual-targeting strategy for MDM2 and XIAP.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Zhijia Wang, Hanxuan Li, Lantu Gou, Wei Li, Yuxi Wang
Summary: Antibody-drug conjugates (ADCs) combine the advantages of monoclonal antibodies and drugs, showing great clinical potential. The payload of ADC drugs plays a crucial role in determining their efficacy, leading to significant research advancements and the development of novel efficient payloads with diverse targets and reduced side effects.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Chemistry, Medicinal
Satyanarayana Pochampally, Kelli L. Hartman, Rui Wang, Jiaxing Wang, Mi-Kyung Yun, Keyur Parmar, Hyunseo Park, Bernd Meibohm, Stephen W. White, Wei Li, Duane D. Miller
Summary: By modifying the pyrimidine dihydroquinoxalinone scaffold, we discovered a new tubulin-polymerization inhibitor, compound 12k, that exhibited potent anticancer activity and significant tumor growth inhibition in vivo.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Cell & Tissue Engineering
Zhousheng Xiao, Li Cao, Micholas Dean Smith, Hanxuan Li, Wei Li, Jeremy C. Smith, Leigh Darryl Quarles
Summary: This study demonstrates the interaction between polycystin-1 and Wwtr1 in osteoblasts and their role in mechanosensing and bone formation. The loss of both proteins results in greater reductions in bone mass and impaired mechanical loading responses. The findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex and could be a potential therapeutic target for osteoporosis.
