Article
Chemistry, Medicinal
Yulong He, Shunyi Li, Yueyue Zhu, Yujie Wang, Yuqi Chen, Deqiang Zhang, Heyao Wang, Yingxia Li
Summary: Fatty-acid binding protein 4 (FABP4) is a crucial factor in the progression of metabolic-related inflammatory diseases, but there is a lack of clinically available FABP4 inhibitors due to their poor selectivity, efficacy, and physicochemical properties. This study presents the systematic optimization of biphenyl scaffold molecules as potent FABP4 inhibitors. Compound 10g was identified as a selective and orally bioavailable inhibitor, with promising anti-inflammatory efficacy and multi-organ protection in an inflammatory mouse model.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shravan Morla, Ongolu Ravikumar, Connor O'Hara, Rio Boothello, Alberto Vera, Elsamani I. Abdelfadiel, Rawan Fayyad, Daniel K. Afosah, Chetna Sharon, Leopoldo Fernandez, Syed Ammer Shah, Bhaumik B. Patel, Umesh R. Desai
Summary: Conjugating cholesterol to synthetic sulfated glycosaminoglycan (GAG) mimetics enables oral delivery and shows excellent anticancer potential both in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Agriculture, Multidisciplinary
Meijun Chen, Zhong Li, Xusheng Shao, Peter Maienfisch
Summary: Dimpropyridaz is a novel insecticide with excellent activity against sucking pests. By designing and synthesizing a series of analogues, the impact of bioisosteric heterocyclic replacements on biological activity and molecular properties was investigated. Computational analysis provided insights into the important role of the 4-pyridazinyl heterocyclic moiety in the insecticide's mechanism of action.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Saroj Kumar Rout, Agonist Kastrati, Harish Jangra, Kuno Schwaerzer, Alisa S. Sunagatullina, Maximilien Garny, Fabio Lima, Cara E. Brocklehurst, Konstantin Karaghiosoff, Hendrik Zipse, Paul Knochel
Summary: DFT calculations can predict the reactivity of uncommon N-heterocyclic scaffolds and facilitate their functionalization. Experimental results show that specific catalysts and reagents can achieve the regioselective derivatization of these compounds.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Medicinal
Minh H. Nguyen, Hai -Fen Ye, Yao Xu, Lisa Truong, April Horsey, Peng Zhao, Evan D. Styduhar, Michelle Frascella, Lynn Leffet, Kelly Federowicz, Elham Behshad, Anlai Wang, Ke Zhang, Michael R. Witten, Chao Qi, Ravi Jalluri, Cheng-Tsung Lai, Onur Atasoylu, Jennifer J. Harris, Rodrigo Hess, Luping Lin, Guofeng Zhang, Maryanne Covington, Sharon Diamond, Wenqing Yao, Oleg Vechorkin
Summary: This study discovered dual FGFR2/FGFR3 inhibitors by repurposing a previously reported ALK2 tool compound. Structure-based drug design and structure-activity relationship studies were used to identify selective and orally bioavailable inhibitors with equipotent activity towards wild-type kinases and a clinically observed gatekeeper mutant.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Zongbao Ding, Wei Pan, Yao Xiao, Binbin Cheng, Gang Huang, Jianjun Chen
Summary: DK1 is a novel DNA-PK inhibitor with great potential for further study. It has favorable drug-like properties and in vivo pharmacokinetics as an oral drug candidate. When used in combination with doxorubicin, DK1 shows synergistic antiproliferative activity against various cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Xiangping Deng, Baohua Xie, Qiuzi Li, Yuan Xiao, Zhiye Hu, Xiaofei Deng, Pingping Fang, Chune Dong, Hai-Bing Zhou, Jian Huang
Summary: This study identified a new ER modulator, 34b, which showed antiproliferative effects against breast cancer cells and induced apoptosis through mitochondrial dysfunction. In vivo experiments demonstrated that 34b had better tumor suppression than tamoxifen. Therefore, this compound has potential as a candidate for treating breast cancer, particularly tamoxifen-resistant breast cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Biswajit Kundu, Deblina Raychaudhuri, Ayan Mukherjee, Bishnu Prasad Sinha, Dipika Sarkar, Purbita Bandopadhyay, Sourav Pal, Nirmal Das, Debdeep Dey, Kantubhukta Ramarao, Kasireddy Nagireddy, Dipyaman Ganguly, Arindam Talukdar
Summary: The study highlights the importance of C2, C6, and N9 substitutions in the purine scaffold for antagonism to TLR7 and TLR9. A lead compound 29 with promising in vivo antagonism efficacy against mouse TLR9 and therapeutic efficacy in a preclinical murine model of psoriasis is identified as a potential therapeutic candidate in relevant autoimmune contexts.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Seddigheh Sheikhi-Mohammareh, Fatemeh Oroojalian, Hamid Beyzaei, Mohammadreza Moghaddam-Manesh, Alireza Salimi, Fatemeh Azizollahi, Ali Shiri
Summary: An efficient one-pot two-step procedure was established for the synthesis of novel pyrazolo[5,1:2,3']pyrimido[4,5':5,6][1,4]thiazino[2,3-b]quinoxalines from easily accessible starting materials. The synthesized compounds showed significant antioxidant activity and can be used as fluorescent markers and probes in biochemistry and pharmacology studies.
Article
Biochemistry & Molecular Biology
Gulshan Kumar, Chinmay Das, Ayan Acharya, Subhasmita Bhal, Mayank Joshi, Chanakya Nath Kundu, Angshuman Roy Choudhury, Sankar K. Guchhait
Summary: A Nature-to-new strategy was employed to investigate analogs of natural aurones, using iterative scaffold-hopping. A method based on organocatalyzed umpolung chemistry was established for the synthesis of (Z)-2-Arylideneimidazo [1,2-a]pyridinones and (Z)-2-Arylidenebenzo[d]imidazo[2,1-b]thiazol-3-ones. Biophysical experiments demonstrated the significant biological properties of these analogs, particularly their anticancer activities.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Sumathy Arunachalam, Suresh Ramalingam, Gowrishankar Narayanasamy Lachmanan, Srinivasan Nagarajan
Summary: Novel pyrazolone fused thiazolidinone analogues were successfully synthesized and evaluated for their inhibition of human breast adenocarcinoma cells. Compound 4B5 showed the highest anticancer properties and has the potential to be developed as a new anti-breast cancer agent.
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Sumathy Arunachalam, Suresh Ramalingam, Gowrishankar Narayanasamy Lachmanan, Srinivasan Nagarajan
Summary: Breast cancer is among the most common types of cancer in women, with HER2-positive breast cancer being widely seen and requiring effective treatment. In this study, novel core scaffold pyrazolone fused thiazolidinone derivatives were synthesized and showed promising anticancer activity in vitro experiments.
JOURNAL OF PHARMACEUTICAL RESEARCH INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Richard Kuan-Lin Lee, Tian-Neng Li, Sui-Yuan Chang, Tai-Ling Chao, Chun-Hsien Kuo, Max Yu-Chen Pan, Yu-Ting Chiou, Kuan-Ju Liao, Yi Yang, Yi-Hsuan Wu, Chen-Hao Huang, Hsueh-Fen Juan, Hsing-Pang Hsieh, Lily Hui-Ching Wang
Summary: This study developed a new method to detect the molecular interaction between the receptor-binding domain (RBD) of SARS-CoV-2 and the ACE2 receptor, and identified two drugs, Etravirine and Dolutegravir, as effective entry inhibitors against SARS-CoV-2. These drugs showed similar neutralizing activities against different variants of the virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Chih-Ming Chen, Hsing-Pang Hsieh
Summary: The Diels-Alder adducts of masked ortho-benzoquinone (MOB) exhibit high regio- and stereoselectivity and can be formed under mild conditions. MOB has various functional groups, is easily accessible, and can be used for complex structure construction through chemical transformations. Therefore, MOB is considered an important intermediate for total synthesis of natural products.
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Gollagani Vijaya Bhavani, Sree Karani Kondapuram, Aifa Fathima Shamsudeen, Mohane Selvaraj Coumar, Joseph Selvin, Tharanikkarasu Kannan
Summary: Novel isoniazid-based pyridinium salts were designed, synthesized, and tested for their antimycobacterial activities, and 4k, 4l, and 7d showed exceptional activities. In vitro and in silico studies suggested that 4k is a potentially promising lead compound for the development of antitubercular candidates.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Chemistry, Medicinal
Mu-Chun Li, Mohane Selvaraj Coumar, Shu-Yu Lin, Yih-Shyan Lin, Guan-Lin Huang, Chun-Hwa Chen, Tzu-Wen Lien, Yi-Wen Wu, Yen-Ting Chen, Ching-Ping Chen, Yu-Chen Huang, Kai-Chia Yeh, Chen-Ming Yang, Bikashita Kalita, Shiow-Lin Pan, Tsu-An Hsu, Teng-Kuang Yeh, Chiung-Tong Chen, Hsing-Pang Hsieh
Summary: The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is discussed. The selectivity for mutant EGFR was achieved by replacing the (S)-2-phenylglycinol moiety with either an ethanol or an alkyl substituent. The optimized lead compound 52 displayed selective inhibition of cancer cells overexpressing EGFRL858R/T790M and showed in vivo antitumor effects in mouse xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ying-Ting Hsu, Shen-Ren Chen, Yung-Chiao Chang, Hsiao-Fu Chang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Hsing-Pang Hsieh, Shau-Hua Ueng, Shiu-Hwa Yeh
Summary: The demand for a non-addictive analgesic medication is increasing due to clinical misuse. Compound 14 is a dual agonist of the mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor, providing pain relief at very small doses and reducing unwanted side effects. Evaluating its effects in wild type and humanized mice can help develop a safer prescription analgesic drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Environmental Sciences
Paola Brinez-Gallego, Dennis Guilherme da Costa Silva, Ana Paula Horn, Mariana Appel Hort
Summary: This study aimed to investigate the effects of curcumin on L-DOPA induced toxicity. The results suggest that curcumin improves motor impairment induced by L-DOPA and reduces levels of reactive oxygen species and lipid peroxidation products in zebrafish larvae.
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
(2023)
Article
Chemistry, Organic
Chih-Ming Chen, Sheng-Kuo Lin, Chi-Tien Hsieh, Julakanti Satyanarayana Reddy, Yi Ning Teoh, Mu-Jeng Cheng, Hsing-Pang Hsieh
Summary: An acyl radical reaction of bicyclo[2.2.2]octenone is described, which can yield rearranged or cyclized isotwistane products. The influence of ring strain on the reaction was demonstrated. DFT calculations showed that the reaction is under thermodynamic control and proceeds via a 5-exo-trig cyclization intermediate, which can undergo either hydrogen-atom transfer to give a cyclized product or rearrangement via a twistane intermediate to give a rearranged product.
Article
Chemistry, Medicinal
Mu -Chun Li, Mohane Selvaraj Coumar, Shu-Yu Lin, Yih-Shyan Lin, Guan-Lin Huang, Chun-Hwa Chen, Tzu-Wen Lien, Yi-Wen Wu, Yen-Ting Chen, Ching-Ping Chen, Yu-Chen Huang, Kai-Chia Yeh, Chen -Ming Yang, Bikashita Kalita, Shiow-Lin Pan, Tsu-An Hsu, Teng-Kuang Yeh, Chiung-Tong Chen, Hsing-Pang Hsieh
Summary: This article describes the development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors. Selectivity for mutant EGFR was achieved by replacing the (S)-2-phenylglycinol moiety of compound 12 with either an ethanol or an alkyl substituent. The lead compound 52 showed 8-fold selectively inhibition of H1975 (EGFR(L858R/T790M) overexpressing) cancer cells and displayed in vivo antitumor effects in two mouse xenograft models with TGI = 74.9% and 97.5% after oral administration (F = 27%).
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Pownraj Brindangnanam, Krishnan Ashokkumar, Sriraghavan Kamaraj, Mohane Selvaraj Coumar
Summary: Antimicrobial resistance (AMR) is a global medical crisis, causing millions of deaths annually. Acinetobacter baumannii, a dangerous nosocomial pathogen, has developed resistance to multiple antibiotics. Blocking drug efflux transporters (DETs) can enhance the efficacy of antibiotics, and a compound called KSA5 has been identified to successfully block antibiotic efflux in A. baumannii. KSA5 has optimal physicochemical and ADME properties, making it a promising candidate for overcoming antimicrobial resistance when combined with antibiotics.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Cell Biology
Monika Kumari, Ruei-Min Lu, Mu-Chun Li, Jhih-Liang Huang, Fu-Fei Hsu, Shih-Han Ko, Feng-Yi Ke, Shih-Chieh Su, Kang-Hao Liang, Joyce Pei-Yi Yuan, Hsiao-Ling Chiang, Cheng-Pu Sun, I-Jung Lee, Wen-Shan Li, Hsing-Pang Hsieh, Mi-Hua Tao, Han-Chung Wu
Summary: The COVID-19 pandemic continues to be a global health crisis, and while vaccines and therapeutics have been developed, challenges remain in addressing the effectiveness against new variants and supporting clinical trials.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Cell Biology
Jai-Shin Liu, Wei-Kai Fang, Shan-Min Yang, Meng-Chen Wu, Tsan-Jan Chen, Chih-Ming Chen, Tung-Yueh Lin, Kai-Lun Liu, Chien-Ming Wu, Yun-Ching Chen, Chih-Pin Chuu, Ling-Yu Wang, Hsing-Pang Hsieh, Hsing-Jien Kung, Wen-Ching Wang
Summary: Myricetin, identified as a potent alpha-ketoglutarate-type inhibitor, blocks the demethylation activity by KDM4s and reduces the proliferation of both androgen-dependent and androgen-independent CRPC cells. A synergistic cytotoxic effect is observed for the combination of myricetin and enzalutamide on CRPC cells. PLGA-encapsulated myricetin in combination with enzalutamide shows significant antitumor activity in a CRPC xenograft model, suggesting its potential effectiveness for CRPC.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Meeting Abstract
Oncology
Chun H. Cheung, Tzu Y. Lin, Sailu Sarvagalla, Mohane S. Coumar, Siao M. Cheng, Euphemia Leung
Article
Cell Biology
You-Liang Lai, Kai-Hung Wang, Hsing-Pang Hsieh, Wan-Ching Yen
Summary: DBPR114 showed activity against HCC tumor cell proliferation in vitro regardless of p53 alteration status and tumor grade. It induced growth inhibition in HCC cells through apoptosis induction, cell cycle arrest, and polyploidy formation. DBPR114 also exhibited anti-angiogenic effects and significantly inhibited tumor growth in multiple HCC tumor xenograft models.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
