Article
Chemistry, Medicinal
Minghua Yuan, Jingtian Su, Yixin Zhang, Jinling Qin, Hua Yang, Yongtao Duan, Yongfang Yao, Moran Sun
Summary: Compound 8p is an effective tubulin inhibitor that disrupts the network structure of microtubules, induces tumor cell apoptosis, arrests cell cycle, and inhibits tumor cell migration and invasion.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Chemistry, Medicinal
Bharat Goel, Shivani Jaiswal, Shreyans K. K. Jain
Summary: Microtubules are important intracellular targets for anticancer activity. Various drugs, such as paclitaxel and vinblastine, act by altering the dynamics of microtubules. In this study, the potential of indole derivatives as colchicine-binding site inhibitors is reviewed. These derivatives have shown the ability to inhibit cancer cell proliferation, induce apoptosis, and disrupt microtubule formation. Understanding the structure-activity relationship of these compounds could lead to the development of novel and effective cancer therapies.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Nisha Schwarz, Sanuja Fernando, Yung-Chih Chen, Thalia Salagaras, Sushma. R. R. Rao, Sanuri Liyanage, Anna. E. E. Williamson, Deborah Toledo-Flores, Catherine Dimasi, Timothy. J. J. Sargeant, Jim Manavis, Eleanor Eddy, Peter Kanellakis, Peter. L. L. Thompson, Joanne T. M. Tan, Marten. F. F. Snel, Christina. A. A. Bursill, Stephen. J. J. Nicholls, Karlheinz Peter, Peter. J. J. Psaltis
Summary: Colchicine has been found to reduce plaque formation and modify plaque composition in murine atherosclerosis. It also inhibits macrophage responses to atherogenic stimuli, decreases inflammation, and stabilizes plaques. These findings support the repurposing of colchicine for atherosclerotic cardiovascular disease.
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
Laura Gallego-Yerga, Andrea Jazmin Chiliquinga, Rafael Pelaez
Summary: Increasing awareness of the structure of microtubules has driven research on targeting tubulin for novel chemotherapies, particularly for glioblastoma multiforme (GBM) cells. Optimization of potently anti-tubulin drugs with improved pharmacokinetic properties is challenging, but the use of ensemble pharmacophore screening has led to the development of a new tetrazole-based tubulin inhibitor. This inhibitor demonstrated remarkable antimitotic effects against various cancer cells, especially GBM cells, with high selectivity and overcome the limitations typically associated with tubulin binding agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Xiang-Yu Yan, Jia-Fu Leng, Ting-Ting Chen, Yong-Jun Zhao, Ling-Yi Kong, Yong Yin
Summary: A series of novel diphenylamine derivatives were synthesized and evaluated for their anti-proliferative activities against human cancer cell lines. Among them, compound 5f exhibited promising anti-proliferative activity against HT29 cells and showed inhibitory effects on cancer cell migration, colony formation, and angiogenesis. Further studies revealed that compound 5f inhibited tubulin polymerization, arrested HT29 cell cycle, induced cell apoptosis, and inhibited tumor growth in animal models. The compound also demonstrated good pharmacokinetic properties. These findings suggest that compound 5f has potential as an antitumor candidate and warrants further investigation.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cardiac & Cardiovascular Systems
Emily F. Warner, Yang Li, Xuan Li
Summary: This review examines the functions of microtubules in the cardiovascular system and their role in cardiac disorders. Currently, there are limited treatments targeting microtubule-relevant mechanisms, but microtubule-targeting drugs show promise as future therapeutic options for heart diseases.
CIRCULATION RESEARCH
(2022)
Article
Chemistry, Medicinal
Bao Cheng, Guirong Zhu, Linghua Meng, Guolin Wu, Qin Chen, Shengming Ma
Summary: In this study, a novel compound dxy-1-175 with potent anticancer activity was discovered by modifying the structure of the compound. It was found to inhibit cancer cell proliferation by interacting with tubulin and was able to overcome multidrug resistance. The improved compound 12e showed superior inhibitory effects on tumor growth in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Wei Liu, Youyou He, Zhongjie Guo, Miaomiao Wang, Xiaodong Han, Hairui Jia, Jin He, Shanshan Miao, Shengzheng Wang
Summary: The study aimed to design and optimize analogues of 2-aryl-4-amide-quinoline derivatives targeting the colchicine binding site of tubulin. Analogues C1 similar to J2 were obtained with diverse substituents and scaffolds. Among them, G13 analogue with a hydroxymethyl group exhibited good tubulin polymerisation inhibitory activity (IC50 = 13.5 μM) and potent antiproliferative activity (IC50 values: 0.65 μM to 0.90 μM). G13 effectively inhibited migration, invasion, and angiogenesis of MDA-MB-231 cells, and induced intracellular ROS increase, MMP decrease, and microtubule network fragmentation and disassembly. Moreover, G13 demonstrated significant in vivo antitumour efficacy in MDA-MB-231 xenograft model (TGI = 38.2%; i.p., 30 mg/kg).
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Wei Liu, Hairui Jia, Minghao Guan, Minxuan Cui, Zhuxuan Lan, Youyou He, Zhongjie Guo, Ru Jiang, Guoqiang Dong, Shengzheng Wang
Summary: In this study, a novel tubulin inhibitor E27 was discovered through structural optimization. E27 demonstrated significant antitumor activity, inhibition of cancer cell migration, induction of apoptosis, and cell cycle arrest.
BIOORGANIC 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
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
Feng-Wei Xia, Bing-Wei Guo, Yu Zhao, Jia-Li Wang, Yuan Chen, Xiu Pan, Xin Li, Jia-Xing Song, Yu Wan, Shun Feng, Ming-Yu Wu
Summary: This study develops a glycan-targeting photosensitizer, ACR-DMP, to fight against stubborn biofilms. ACR-DMP has high extracellular polymer penetrability and overcomes the hypoxic microenvironment, efficiently eradicating biofilms in vitro and in vivo. It not only changes membrane potential homeostasis and osmotic pressure balance, but also inhibits quorum sensing, two-component system, and efflux pump to conquer biofilm resistance.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Physical
Mohammed Hawash, Deniz Cansen Kahraman, Abdurrahman Olgac, Sezen Guntekin Ergun, Ernest Hamel, Rengul Cetin-Atalay, Sultan Nacak Baytas
Summary: In this study, novel compounds with polar and nonpolar substitutions on the prop-2-en-1-on linker of the trans-indol-3-ylacrylamide scaffold were designed and synthesized. The antiproliferative activities of these compounds against hepatocellular carcinoma were evaluated, and five of the compounds showed moderate antitumor activities. Compound 13 was identified as a tubulin polymerization inhibitor and induced G2/M-phase arrest in Huh7 cells. The results suggest that polar substitutions enhance the potency against tubulin polymerization.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Medicinal
Domiziana Masci, Michela Puxeddu, Laura Di Magno, Michele D'Ambrosio, Anastasia Parisi, Marianna Nalli, Ruoli Bai, Antonio Coluccia, Pietro Scio, Viviana Orlando, Sara D'Angelo, Stefano Biagioni, Andrea Urbani, Ernest Hamel, Alessio Nocentini, Serena Filiberti, Marta Turati, Roberto Ronca, Joanna Kopecka, Chiara Riganti, Cinzia Fionda, Rosa Bordone, Giorgia Della Rocca, Gianluca Canettieri, Claudiu T. Supuran, Romano Silvestri, Giuseppe La Regina
Summary: We synthesized new compounds as inhibitors of human carbonic anhydrase (hCA) with the potential to inhibit the Wnt/beta-catenin signaling pathway. One of the compounds, designated as compound 15, not only showed strong inhibition against hCA XII, but also suppressed the Wnt/beta-catenin signaling pathway and its target genes. It exhibited potent cytotoxicity against cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Shailendra Singh, Chandrabose Karthikeyan, N. S. Hari Narayana Moorthy
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Neelesh Maheshwari, Chandrabose Karthikeyan, Shraddha Bhadada, Amit K. Verma, Chan-dan Sahi, N. S. Hari Narayana Moorthy, Piyush Trivedi
Summary: This study successfully developed novel PTP1B inhibitors with good enzyme binding affinity and activity through computational methods and biological evaluation studies. The identified compounds showed significant interactions with the active site residues of the PTP1B enzyme, with compounds S1 and S2 exhibiting considerable in vitro PTP1B inhibitory and in vivo antidiabetic activities.
LETTERS IN DRUG DESIGN & DISCOVERY
(2021)
Article
Chemistry, Medicinal
Monika Rakse, Chandrabosc Karthikeyan, Narayana Subbiah Hari Narayana Moorthy, Ram Kishore Agrawal
Summary: The research focused on designing and synthesizing acetamidobenzoic acid derivatives as potential inhibitors of PTP1B for treating Type II diabetes. Compound 4f showed good PTP1B inhibitory activity and anti-hyperglycemic efficacy in STZ-induced diabetic Wistar rats. Docking studies revealed that compound 4f bound effectively to the active site of PTP1B.
LETTERS IN DRUG DESIGN & DISCOVERY
(2021)
Article
Automation & Control Systems
N. S. Hari Narayana Moorthy, Chandrabose Karthikeyan, Elangovan Manivannan
Summary: The study focused on developing novel bioactive molecules without hERG ion channel blocking activities using experimental and in silico techniques. Various machine learning algorithms were applied to analyze the data set, showing that certain MOE-descriptors and MACCS Fingerprints played important roles in predicting the activity. The results indicated that models utilizing these descriptors and fingerprints can be effective in predicting hERG ion channel blocking activities of novel molecules.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2021)
Review
Pharmacology & Pharmacy
Elangovan Manivannan, Chandrabose Karthikeyan, N. S. Hari Narayana Moorthy, Subash Chandra Chaturvedi
Summary: The rapid spread and high mortality rate of COVID-19 have posed a global public health challenge. Chloroquine and hydroxychloroquine were initially considered for the treatment of COVID-19, but their authorization was later revoked by FDA and WHO, emphasizing the need for evidence-based treatment protocols to address the pandemic.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Arvind Kumar Jain, Arindam Gupta, C. Karthikeyan, Piyush Trivedi, Anita Dutt Konar
Summary: This study describes the design and synthesis of a new set of heterocyclic analogs, where compounds IV and V were found to be highly selective towards the target GSK3 beta. Molecular modeling studies revealed a primary H-bonding between compounds IV/V and Val 135 residue in the receptor GSK3 beta, with other non-covalent interactions potentially enhancing target selectivity.
CHEMISTRY & BIODIVERSITY
(2021)
Article
Biochemistry & Molecular Biology
Rabin Neupane, Saloni Malla, Mariam Sami Abou-Dahech, Swapnaa Balaji, Shikha Kumari, Digambar Kumar Waiker, N. S. Hari Narayana Moorthy, Piyush Trivedi, Charles R. Ashby, Chandrabose Karthikeyan, Amit K. Tiwari
Summary: The novel 4-anilinoquinazoline analogues, particularly DW-8, showed high anticancer efficacy and selectivity in colorectal cancer cell lines by inducing cell cycle arrest and activating the apoptotic pathway. Their potential as lead compounds for developing novel treatments for colorectal cancer is promising.
Article
Biochemistry & Molecular Biology
Jenna M. Len, Noor Hussein, Saloni Malla, Kyle Mcintosh, Rahul Patidar, Manivannan Elangovan, Karthikeyan Chandrabose, N. S. Hari Narayana Moorthy, Manoj Pandey, Dayanidhi Raman, Piyush Trivedi, Amit K. Tiwari
Summary: The novel compound DML6 showed selective and significant anti-proliferative effects on cervical cancer cells, inducing apoptosis. It arrested cell cycle at G2 phase, increased reactive oxygen species level, and disrupted mitochondrial membrane potential. DML6 also modulated the expression of apoptotic proteins and activated caspases, leading to cancer cell death. Further evaluation of DML6 as a potential treatment for cervical cancer is warranted.
Article
Multidisciplinary Sciences
James Knockleby, Aicha Dede Djigo, Indeewari Kalhari Lindamulage, Chandrabose Karthikeyan, Piyush Trivedi, Hoyun Lee
Summary: Compounds targeting tubulin as potential anticancer agents have shown promising efficacy and safety, with CTR-21 and CTR-32 identified as lead compounds that effectively kill a variety of cancer cells, including multi-drug resistant cells, and exhibit high selectivity against cancer cells. These compounds prevent tubulin polymerization and induce cell cycle arrest at G2/M, with CTR-21 demonstrating more favorable metabolic properties and showing synergistic effects when combined with the Bcl-2 inhibitor ABT-737.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Shailendra Singh, Chandrabose Karthikeyan, Narayana Subbiah Hari Narayana Moorthy
Summary: Fatty acid synthase (FASN), an important enzyme in fatty acid biosynthesis, is upregulated in various cancer cells. This study identified a series of compounds with FASN inhibitory activity and found that the topological properties of the molecules played a key role in activity classification. The presence of heteroatoms and hydrogen bond acceptor groups also actively contributed to the inhibitory activities.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Biochemistry & Molecular Biology
Arvind Kumar Jain, Arindam Gupta, C. Karthikeyan, Piyush Trivedi, Anita Dutt Konar
Summary: A set of new heterocyclic analogs were synthesized and tested for their activity against CDK5. Analysis showed that compounds III and VI were the most potent, supported by Density Functional Theory calculations and molecular modeling studies. However, the activity of these compounds on other kinases was not significant.
CHEMISTRY & BIODIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Chanchal Kiran Thakur, Rabin Neupane, Chandrabose Karthikeyan, Charles R. Ashby, R. Jayachandra Babu, Sai H. S. Boddu, Amit K. Tiwari, Narayana Subbiah Hari Narayana Moorthy
Summary: A simple and cost-effective method was reported to functionalize MWCNTs with carbohydrate ligands using lysine as a linker. The results showed that carbohydrate-modified MWCNTs had higher drug loading capacity and improved anticancer efficacy.
Review
Pharmacology & Pharmacy
Chanchal Kiran Thakur, Chandrabose Karthikeyan, Mariam Sami Abou-Dahech, Moawia Mohd A. M. Altabakha, Moayad Jamal Saeed Al Shahwan, Charles R. R. Ashby Jr, Amit K. Tiwari, R. Jayachandra Babu, Narayana Subbiah Hari Narayana Moorthy
Summary: Microwave-assisted synthetic methods are commonly used for the surface modification and functionalization of multi-walled carbon nanotubes (MWCNTs) in diverse drug delivery applications. Microwave-induced functionalization of MWCNTs offers high efficiency and shorter reaction time compared to conventional techniques. Microwave methods are simple, fast, and effective for the covalent and noncovalent conjugation of MWCNTs with various biomolecules and polymers. This review focuses on the synthesis and drug delivery applications of microwave irradiation techniques (MITs) for the functionalization of MWCNTs using amino acids, vitamins, proteins, epoxy moieties, metal nanoparticles, and polymers.
Article
Biology
Swapnaa Balaji, Rabin Neupane, Saloni Malla, Rahul Khupse, Haneen Amawi, Shikha Kumari, Diwakar Bastihalli Tukaramrao, Srestha Chattopadhyay, Charles R. Ashby Jr, Sai H. S. Boddu, Chandrabose Karthikeyan, Piyush Trivedi, Dayanidhi Raman, Amit K. Tiwari
Summary: Prostate cancer is the most common cancer in men, and the study suggests that IND-2 may be a potential lead compound for the treatment of prostate cancer, with effects such as inhibiting cell proliferation, inducing apoptosis, and causing mitotic catastrophe.
Review
Chemistry, Multidisciplinary
Monu Kumar Shukla, Arpana Parihar, Chandrabose Karthikeyan, Deepak Kumar, Raju Khan
Summary: This review discusses the potential of multifunctional graphene quantum dots (GQDs) as a platform for receptor targeting, drug delivery, and bioimaging in pancreatic cancer. GQDs have the ability to selectively target pancreatic cancer cells and serve as drug delivery vehicles for controlled and targeted release of therapeutics. Additionally, GQDs show promise as imaging agents for pancreatic cancer detection and monitoring.