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
Bulian Deng, Zhiqiang Sun, Yuxi Wang, Ruiyao Mai, Zichao Yang, Yichang Ren, Jin Liu, Junli Huang, Zeli Ma, Ting Chen, Canjun Zeng, Jianjun Chen
Summary: This study designed a series of novel imidazo[1,2-a]pyrazine derivatives as potential tubulin inhibitors through structural optimization and ring fusion strategy. Among them, compound TB-25 exhibited the strongest inhibitory effects against HCT-116 cells. It could effectively inhibit tubulin polymerization and destroy the dynamic equilibrium of microtubules in cells, induce G2/M phase cell cycle arrest and apoptosis, and suppress cell migration.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Irina Tolmacheva, Yulia Beloglazova, Mikhail Nazarov, Olga Gagarskikh, Victoria Grishko
Summary: Multidrug resistance (MDR) is a common occurrence in cancer treatment, where cancer cells become resistant to chemotherapy drugs due to overexpression of ATP-binding cassette efflux transporters, including P-glycoprotein (P-gp). A new semi-synthetic derivative, MK, was found to have the highest cytotoxicity against cancer cells, but it was not identified as a P-gp inhibitor or substrate. Further studies suggest that the cytotoxic effect of MK on cancer cells may be induced through the ROS-mediated mitochondrial pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Greta Klejborowska, Alicja Urbaniak, Ewa Maj, Joanna Wietrzyk, Mahshad Moshari, Jordane Preto, Jack A. Tuszynski, Timothy C. Chambers, Adam Huczynski
Summary: Colchicine and its derivatives are considered promising lead compounds for chemotherapy agents against various types of cancer, showing activity against multiple cancer cell lines and exhibiting contrasting effects in cell cycle analysis.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
David S. P. Cardoso, Annamaria Kincses, Marta Nove, Gabriella Spengler, Silva Mulhovo, Joao Aires-de-Sousa, Daniel J. V. A. dos Santos, Maria-Jose U. Ferreira
Summary: This study aimed to enhance multidrug resistance (MDR) reversing activity in cancer by deriving new compounds from major epimeric alkaloids isolated from Tabernaemontana elegans. The derivatives showed increased activity, with those containing N-phenethyl moieties exhibiting the strongest P-glycoprotein inhibitory effects. Synergistic interactions with the antineoplastic drug doxorubicin were observed, highlighting the potential of these compounds as MDR reversers. Lipophilicity and bulkiness features were associated with inhibitory activity based on the explored QSAR models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Ya-Xin Sun, Jian Song, Li-Jun Kong, Bei-Bei Sha, Xin-Yi Tian, Xiu-Juan Liu, Tao Hu, Ping Chen, Sai-Yang Zhang
Summary: This study designed a series of novel bis-substituted aromatic amide dithiocarbamate derivatives as tubulin inhibitors with potential anticancer activities. Among them, compound 20q exhibited the most potent antiproliferative activity and was identified as a tubulin inhibitor targeting the colchicine binding site.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Thermodynamics
Sandra Ramos-Inza, Eneko Almagro, Maria Font, Ignacio Encio, Daniel Plano, Carmen Sanmartin, Rafael Sirera, Elena Lizarraga
Summary: In this study, the stability, thermal characterization, and polymorphic forms of thirty new nonsteroidal anti-inflammatory drug derivatives containing selenium were analyzed. The compounds exhibited thermal stability and no significant differences were found among polymorphic forms, indicating their suitability for further drug development.
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
(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
Chemistry, Medicinal
Rong Zeng, Xiu-Ming Yang, Xue Li, Yu Guan, Tao Yu, Peng Yan, Wen Yuan, Sheng-Li Niu, Jing Gu, Ying-Chun Chen, Qin Ouyang
Summary: In this study, a simplified compound OY-101 was developed as a specific and efficient P-gp inhibitor with high reversal activity and low cytotoxicity. The OY-101 showed excellent synergistic anti-cancer effect with vincristine against drug-resistant cells without obvious toxicity, suggesting its potential as an anti-tumor chemotherapy sensitizer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Mayank, Ashutosh Singh, Kumar Udit Saumya, Mayank Joshi, Navneet Kaur, Neha Garg, Narinder Singh
Summary: 4H-Chromene derivatives are potential anticancer compounds that bind to the colchicine binding site of tubulin protein. The 2-amino-4-phenyl-4H-benzo[h]chromene-3-carbonitrile-based 4H-chromenes scaffold has a significant impact on tubulin proteins. Understanding the interaction pattern of these compounds against various tubulin isoforms is important for selective targeting of cancer cells. Structural modification can potentially enhance the selective targeting ability of these molecules.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Laura Braconi, Silvia Dei, Marialessandra Contino, Chiara Riganti, Gianluca Bartolucci, Dina Manetti, Maria Novella Romanelli, Maria Grazia Perrone, Nicola Antonio Colabufo, Stefano Guglielmo, Elisabetta Teodori
Summary: New 2,5- and 1,5-disubstituted tetrazoles, and 2,5-disubstituted-1,3,4-oxadiazoles were synthesized and studied as MDR reversers, showing potent inhibitory effects on P-gp transport activity and increasing the antiproliferative effect of doxorubicin in MDR cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Wenjun Yu, Xilei Xie, Yao Ma, Shiping Fang, Yi Dong, Gang Liu
Summary: In this study, a random screening of multiple human tumor cell lines was performed to identify potential anti-tumor compounds. A hit compound, 1,4-benzodiazepine-2,5-dione (BZD, 11a), was found to effectively inhibit the growth of various human cancer cell lines. Further investigation revealed that a synthetic compound, 52b, with a similar structure as BZD, exerted potent anti-tumor effects by inhibiting protein synthesis in lung cancer cells. In vivo experiments showed that 52b significantly prevented tumor growth in a mouse model without causing toxic effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Seyed-Omar Zaraei, Nour N. Al-Ach, Hanan S. Anbar, Randa El-Gamal, Hamadeh Tarazi, Rimas T. Tokatly, Rawan R. Kalla, Mouna A. Munther, Marwa M. Wahba, Aya M. Alshihabi, Mahmoud K. Shehata, Rawan M. Sbenati, Afnan I. Shahin, Raafat El-Awady, Taleb H. Al-Tel, Mohammed I. El-Gamal
Summary: This article presents the design, synthesis, and biological screening results of a new series of diarylurea and diarylamide derivatives with a quinoline core armed with dimethylamino or morpholino side chains. The compounds showed broad-spectrum antiproliferative activity against a panel of 60 cancer cell lines, with three of them demonstrating higher potency than the reference drug, sorafenib. The compounds also exhibited high selectivity for C-RAF kinase, making them potential inhibitors for this molecular target.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Olga Michalak, Marcin Cybulski, Wojciech Szymanowski, Agnieszka Gornowicz, Marek Kubiszewski, Kinga Ostrowska, Piotr Krzeczynski, Krzysztof Bielawski, Bartosz Trzaskowski, Anna Bielawska
Summary: A series of new derivatives of ursolic acid (UA) were designed and synthesized by substituting various amino acids (AAs) or dipeptides (DP) at the C-3 position of the steroid skeleton. These conjugates exhibited cytotoxic activity against hormone-dependent and triple-negative breast cancer cells. Mechanistic studies revealed the activation of apoptotic pathways for some compounds and the induction of autophagy for others. Additionally, the synthesized compounds showed potential as anticancer agents based on their ADME properties and molecular docking to the estrogen receptor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Maxim E. Zhidkov, Moritz Kaune, Alexey Kantemirov, Polina A. Smirnova, Pavel Spirin, Maria A. Sidorova, Sergey A. Stadnik, Elena Y. Shyrokova, Dmitry N. Kaluzhny, Oleg A. Tryapkin, Tobias Busenbender, Jessica Hauschild, Tina Rohlfing, Vladimir S. Prassolov, Carsten Bokemeyer, Markus Graefen, Gunhild von Amsberg, Sergey A. Dyshlovoy
Summary: We synthesized a library of fascaplysin derivatives and investigated their selectivity, effects on cells, and DNA intercalation. The di- and trisubstituted halogen derivatives showed pronounced selectivity for cancer cells, while modification of cycle C resulted in stronger activity against therapy-resistant cells.
Article
Chemistry, Medicinal
Rinky Raghuvanshi, Sandip B. Bharate
Summary: Kinases are therapeutic targets involved in various diseases. FDA approved kinase inhibitors have shown potential in treating viral infections and possess broad-spectrum antiviral activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Applied
Maithili N. Kantak, Sonali S. Bharate
Summary: Chitosan, a modified natural carbohydrate polymer, has a wide range of medical and pharmaceutical applications. It can be used as a biomaterial in medical devices and as an excipient, drug carrier, or therapeutic agent in pharmaceuticals. Numerous clinical studies are being conducted to investigate the safety and efficacy of chitosan and its biomaterials/nanoparticles.
CARBOHYDRATE POLYMERS
(2022)
Article
Biochemistry & Molecular Biology
Shanaika J. Devadiga, Sonali S. Bharate
Summary: Huntington's disease is a rare and incurable neurodegenerative disorder. There are only two FDA-approved drugs for managing the symptoms associated with Huntington's disease, while other drugs are used off-label. Currently, drug repurposing and various clinical studies are being conducted to find new treatments for Huntington's disease.
BIOORGANIC CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Ameya Fulmali, Sonali S. Bharate
Summary: The salification and prodrug approaches can optimize the physicochemical properties and pharmacokinetic parameters of drugs. Salification with phosphoric acid enhances water solubility, while phosphate moiety in prodrugs improves permeability. This review focuses on FDA-approved phosphate salts and prodrugs from 1939 to 2021 and discusses their biopharmaceutical advantages over the parent molecules.
DRUG DEVELOPMENT RESEARCH
(2022)
Article
Chemistry, Medicinal
Baljinder Singh, Amrita Sharma, Naresh Gunaganti, Mitch Rivers, Pradip K. Gadekar, Brady Greene, Michael Chichioco, Carlos E. Sanz-Rodriguez, Courtney Fu, Catherine LeBlanc, Erin Burchfield, Nyle Sharif, Benjamin Hoffman, Gaurav Kumar, Andrei Purmal, Kojo Mensa-Wilmot, Michael P. Pollastri
Summary: To develop a candidate drug against human African trypanosomiasis (HAT), researchers synthesized new analogs and evaluated their properties. Eight new compounds with higher or equivalent selectivity indices were identified. Two compounds, 5v and 5w, were tested in a mouse model of HAT, and 5v showed a lead-like profile for drug development while 5w lacked efficacy. These findings will guide further optimization of carbazoles for HAT and other indications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Applied
Abhishek Gour, Ashish Dogra, Mahendra K. Verma, Mahir Bhardwaj, Dilpreet Kour, Ashiya Jamwal, Bapi Gorain, Mukesh Kumar, Bhavna Vij, Ajay Kumar, Utpal Nandi
Summary: The study investigated the protective effect of a herbal compound called NPM on acute lung injury (ALI). Results showed that NPM improved lung damage caused by ALI and had antioxidant and anti-inflammatory effects. The findings provide potential insights into Ayurvedic recommendations for boosting immunity during ALI.
NATURAL PRODUCT RESEARCH
(2023)
Article
Chemistry, Applied
Bashir Ahmad Lone, Nitika Sharma, Dilpreet Kour, Anil Bhushan, Dixhiya Rani, Ajay Kumar, Prashant Kumar Gupta, Prasoon Gupta
Summary: In this study, two compounds, baicalin and naringenin, were identified as potent inhibitors of sickling in SCD patients' blood samples. These flavonoids have shown promising potential for the management of SCD crisis where effective therapy is lacking.
NATURAL PRODUCT RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Vijay K. Nuthakki, Sushil Choudhary, Chilakala N. Reddy, Shipra Bhatt, Ashiya Jamwal, Anshika Jotshi, Rinky Raghuvanshi, Ankita Sharma, Shikha Thakur, Hemant R. Jadhav, Sonali S. Bharate, Utpal Nandi, Ajay Kumar, Sandip B. Bharate
Summary: The complex and multifaceted nature of Alzheimer's disease has led to a demand for ligands that can target multiple pathways. Embelin, a secondary metabolite of Indian traditional herb Embelia ribes Burm f., has been found to inhibit cholinesterases (ChEs) and BACE-1, but it has poor ADME properties. In this study, embelin-aryl/alkyl amine hybrids were synthesized to improve its physicochemical properties and therapeutic potency. The most active derivative, 9j (SB-1448), exhibited inhibitory activity against ChEs and BACE-1, good ADME properties, and protection against scopolamine-induced cell death.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Applied
Suruchi Gupta, Malvi Choudhary, Baljinder Singh, Manoj Kushwaha, Manoj K. Dhar, Sanjana Kaul
Summary: Two compounds, glaucanic acid and dihydrocompactin acid, were isolated from the endophytic fungus Penicillium polonicum and characterized by NMR and mass spectroscopy. Both compounds exhibited antifungal, antioxidant, and cytotoxicity activities. This is the first report on the biological activities of dihydrocompactin acid produced by an endophytic fungal strain.
NATURAL PRODUCT RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Dilpreet Kour, Mehboob Ali, Parul Khajuria, Kuhu Sharma, Palash Ghosh, Sukhleen Kaur, Surbhi Mahajan, P. Ramajayan, Sonali S. Bharate, Subhash Bhardwaj, Sanghapal D. Sawant, D. Srinivasa Reddy, Ajay Kumar
Summary: Sickle cell disease (SCD) is characterized by complications arising from the sickling of erythrocytes due to a point mutation in the beta-globin chain of hemoglobin. Flurbiprofen, a COX-2 inhibitor, was found to be a potent inhibitor of heme-induced NLRP3 inflammasome, providing potential for pain management and disease modification in SCD.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Deepank S. Gupta, Pankul Kotwal, Utpal Nandi, Sonali S. Bharate
Summary: This study explores the potential of beta-cyclodextrin and its derivatives for enhancing the dissolution of niclosamide. Among the cyclodextrins studied, 2-Hydroxypropyl-beta-cyclodextrin in the 1:2 molar ratio shows the most significant improvement in water solubility and in-vitro dissolution of niclosamide. Oral administration of the niclosamide and HP-beta-CD complex in rats resulted in higher plasma exposure. Spectral characterization provides insights into the interactions between niclosamide and HP-beta-CD.
Article
Biochemistry & Molecular Biology
Sadhana Sharma, Sushil Choudhary, Sukhleen Kaur, M. Venkat Reddy, Niranjan Thotac, Amarinder Singh, Surrinder Koul, Inshad Ali Khan, Zabeer Ahmed, Ajay Kumar
Summary: This study synthesized derivatives of dihydronaphthyl and evaluated their inhibition activity on P-glycoprotein (P-gp). PGP-41 exhibited the most potent P-gp inhibition activity in colorectal adenocarcinoma LS-180 cells and chemoresistant ovarian cell line NCI/ADR-RES. PGP-41 sensitized NCI/ADR-RES cells to paclitaxel treatment by downregulating P-gp expression and increasing intracellular concentration of paclitaxel.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Chetan Kumar, Gourav Chandan, Manoj Kushwaha, Amit Kumar, Sukhleen Kaur, Ajay Kumar, Govind Yadav, Sumeet Gairola, Ram A. Vishwakarma, Naresh Kumar Satti, Mahendra Kumar Verma
Summary: The present study isolated, identified, and quantified biomarker compounds in plant extracts of Habenaria intermedia D. Don. The compounds were isolated using column chromatography and characterized using NMR and mass spectral data. A new quantitative method using HPLC-PDA was established, resulting in the isolation and characterization of seven compounds. The study also revealed the immunomodulatory and anti-inflammasome activities of these compounds, suggesting their potential utilization as functional health supplements.
Article
Chemistry, Medicinal
Baljinder Singh, Amrita Sharma, Naresh Gunaganti, Mitch Rivers, Pradip K. Gadekar, Brady Greene, Michael Chichioco, Carlos E. Sanz-Rodriguez, Courtney Fu, Catherine LeBlanc, Erin Burchfield, Nyle Sharif, Benjamin Hoffman, Gaurav Kumar, Andrei Purmal, Kojo Mensa-Wilmot, Michael P. Pollastri
Summary: New analogs of the carbazole CBL0137 were synthesized and evaluated, resulting in the discovery of eight compounds with higher or equivalent selectivity indices. Among them, 5v demonstrated potential for drug development against human African trypanosomiasis (HAT), while 5w showed lack of efficacy. Lessons from these studies will guide further optimization of carbazoles for HAT and other indications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Correction
Chemistry, Multidisciplinary
Shreyans K. Jain, Anup S. Pathania, Rajinder Parshad, Chandji Raina, Asif Ali, Ajai P. Gupta, Manoj Kushwaha, Subrayashastry Aravinda, Shashi Bhushan, Sandip B. Bharate, Ram A. Vishwakarma
Summary: Correction is made for the study on the antileukemic naphthocoumarins, Chrysomycins A-C, from Streptomyces sporoverrucosus by Shreyans K. Jain et al. in 2013. The authors further discovered new antileukemic synthetic compounds from the Streptomyces sporoverrucosus and characterized them.
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)