Review
Biochemistry & Molecular Biology
Giulia Coffetti, Martina Moraschi, Giorgio Facchetti, Isabella Rimoldi
Summary: One of the main problems in chemotherapy using platinum drugs as anticancer agents is the resistance phenomenon. Synthesizing and evaluating valid alternative compounds is challenging. This review focuses on the last two years of progress in the studies of platinum (II)- and platinum (IV)-based anticancer complexes, discussing their ability to bypass resistance and the different reaction mechanisms they exhibit compared to cisplatin.
Article
Chemistry, Inorganic & Nuclear
Muneebah Adams, Matthew P. Sullivan, Kelvin K. H. Tong, David C. Goldstone, Muhammad Hanif, Stephen M. F. Jamieson, Christian G. Hartinger
Summary: This study reports a series of platinum complexes that target DNA through coordination and/or alkylation, demonstrating strong antiproliferative activity. Investigations on their aqueous stability and reactivity with various small biomolecules were conducted. Furthermore, protein crystallography identified the binding site of platinum complex PtL3 with the model protein.
INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ruchika Ojha, Peter C. Junk, Alan M. Bond, Glen B. Deacon
Summary: Pt-IV coordination complexes were synthesized by oxidizing the antitumor agent [Pt-II(p-BrC6F4)NCH2CH2NEt2}Cl(py)]. Experimental data showed that excess H2O2 and elevated temperature favored the oxidation of the ligand, while a smaller amount of H2O2 at room temperature favored the oxidation of the metal, resulting in the formation of platinum(IV) complexes.
Article
Chemistry, Multidisciplinary
Qiyuan Zhou, Shu Chen, Zoufeng Xu, Gongyuan Liu, Shuyuan Zhang, Zhigang Wang, Man-Kit Tse, Shek-Man Yiu, Guangyu Zhu
Summary: This study reports the synthesis of Pt-IV complexes bearing axial pyridines through ligand exchange reactions. It was discovered that these axial pyridines can be quickly released after reduction, indicating their potential as axial leaving groups. Two multitargeted Pt-IV prodrugs containing bioactive pyridinyl ligands, a PARP inhibitor and an EGFR tyrosine kinase inhibitor, were successfully obtained using this method. These conjugates show great potential for overcoming drug resistance, with the latter inhibiting the growth of Pt-resistant tumor in vivo. This research expands the synthetic methods for Pt-IV prodrugs and increases the range of bioactive axial ligands that can be conjugated to a Pt-IV center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Inorganic & Nuclear
Juan Sanchez-Camacho, Sonia Infante-Tadeo, Ana C. Carrasco, Stefano Scoditti, A'lvaro Martinez, Fabienne Barroso-Bujans, Emilia Sicilia, Ana M. Pizarro, Luca Salassa
Summary: In this study, two new asymmetric Pt(IV) derivatives were designed and synthesized, which could be effectively activated into toxic Pt(II) species by incubation with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. One of the derivatives displayed enhanced toxicity in MDA-MB-231 breast cancer cells preincubated with ascorbate, suggesting selective triggering of oxaliplatin generation through redox activation. Covalent binding of the flavin to the Pt complex was shown to be pivotal for this effect.
INORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mariafrancesca Hyeraci, Laura Agnarelli, Luca Labella, Fabio Marchetti, Maria Luisa Di Paolo, Simona Samaritani, Lisa Dalla Via
Summary: Resistance to cisplatin limits its usefulness as an anticancer drug. This study describes the synthesis and characterization of two new platinum complexes and demonstrates their potential in overcoming cisplatin resistance in cancer cells. The complexes exhibited poor ability to platinate DNA but showed significant intracellular accumulation. Mechanistic studies revealed their ability to inhibit DNA relaxation and activate the apoptotic pathway. Comparison with related complexes provides insights into the resistance phenotype.
Article
Biochemistry & Molecular Biology
Rui Li, Weiheng Zhao, Chen Jin, Huihua Xiong
Summary: In this study, a series of platinum(IV) complexes with 4-amino-quinazoline as ligands were synthesized and evaluated for their anticancer activities. Among them, 17b exhibited higher cytotoxicity against lung cancer cells and lower cytotoxicity towards normal cells, suggesting it as a novel strategy to overcome resistance to platinum(II) drugs.
BIOORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Martin Vojtek, Clara B. Martins, Raquel Ramos, Sara Gomes Duarte, Isabel M. P. L. V. O. Ferreira, Ana L. M. Batista de Carvalho, M. Paula M. Marques, Carmen Diniz
Summary: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer and current drug treatments often face limitations. In this study, Pd(3)Spd(2) was found to be a promising metal-based anticancer agent for TNBC treatment, surpassing its Pt analog in activity. Pd(3)Spd(2) demonstrated similar antiproliferative activity in both sensitive and resistant TNBC cells and showed a promising selectivity index ratio, indicating its potential for further exploration in treating TNBC and its cisplatin-resistant forms.
Article
Biochemistry & Molecular Biology
Jana Hildebrandt, Norman Hafner, Daniel Kritsch, Helmar Goerls, Matthias Duerst, Ingo B. Runnebaum, Wolfgang Weigand
Summary: This study investigates the anticancer activity and resistance evasion ability of 17 ruthenium complexes and four osmium analogues with cinnamic acid derivatives as O,S bidentate ligands. The results show that these compounds exhibit high cancer cell selectivity and cytotoxicity without strong effects on DNA damage and cell cycle, suggesting another mode of action.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Yichang Ren, Yuxi Wang, Gang Li, Zherong Zhang, Lingling Ma, Binbin Cheng, Jianjun Chen
Summary: Novel indazole and benzimidazole analogues, such as compound 12b, demonstrated potent antiproliferative activities against cancer cells, with IC50 values comparable to colchicine. Compound 12b also showed in vivo antitumor efficacy in a melanoma tumor model, suggesting its potential as a promising lead compound for further investigation as a potential anticancer agent.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Inorganic & Nuclear
Ricardo G. Teixeira, Dimas C. Belisario, Xavier Fontrodona, Isabel Romero, Ana Isabel Tomaz, M. Helena Garcia, Chiara Riganti, Andreia Valente
Summary: Platinum-based therapies are the main treatment for non-small cell lung cancers (NSCLC), but multidrug resistance often leads to treatment failure. In this study, two sets of organometallic Ru(II) compounds were synthesized and tested on NSCLC cell lines, showing strong activity against cisplatin-resistant cells by inhibiting transporters MRP1 and P-gp. These compounds act as MDR-selective compounds and have the potential to enhance cisplatin cytotoxicity significantly.
INORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Biochemistry & Molecular Biology
Francesca Sacco, Matteo Tarchi, Giarita Ferraro, Antonello Merlino, Giorgio Facchetti, Isabella Rimoldi, Luigi Messori, Lara Massai
Summary: The study investigated the reactions of three novel platinum(II) complexes with model proteins through ESI MS analysis, revealing diverse reactivity patterns depending on the nature of the Pt complex and interacting proteins. The formation of protein-bound Pt fragments was identified, and crystal structures were used to determine the exact location of Pt binding sites, contributing to understanding the potential mechanisms of action of these innovative anticancer Pt complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Inorganic & Nuclear
Kun Peng, Bing-Bing Liang, Wenting Liu, Zong-Wan Mao
Summary: Research on platinum coordination complexes as anticancer drugs has been conducted for over half a century with the inspiration from the success of cisplatin in cancer chemotherapy. Despite the emergence of numerous promising platinum complexes, most have failed to enter clinical applications. Strategies have been proposed in recent decades to address the complicated reasons for the abandonment of platinum antitumor candidates from experiment to clinic. With advancements in targeted therapy and immunotherapy, anticancer platinum drugs are facing new opportunities and challenges.
COORDINATION CHEMISTRY REVIEWS
(2021)
Review
Engineering, Biomedical
Tianyuan Zhong, Jie Yu, Yong Pan, Ning Zhang, Yanxin Qi, Yubin Huang
Summary: Platinum drugs are widely used in cancer treatment, but their toxicity and drug resistance pose challenges. Combination therapy with platinum drugs can effectively inhibit tumor growth and metastasis, reducing toxicity and overcoming resistance. This review summarizes the current progress and challenges in platinum-based combination therapy, including gene editing, ROS-based therapy, thermal therapy, immunotherapy, and imaging modality. It hopes to inspire researchers for the development of more effective platinum-based anti-cancer complexes in the future.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Chemistry, Medicinal
Meng-Meng Wang, Hao-Ming Li, Dong-Ping Deng, Yan Su, Zhi Su
Summary: This research discusses Ir(III)-based anticancer agents and their potential anticancer mechanisms to inhibit the proliferation of cisplatin-resistant tumors. It could be significant in developing more effective Ir(III)-based agents to combat cisplatin resistance.
Review
Pharmacology & Pharmacy
Mohit Kumar, Pooja A. Chawla, Abdul Faruk, Viney Chawla
Summary: Most new and existing drug candidates are lipophilic, resulting in low bioavailability. Self-emulsifying drug delivery systems (SEDDS) have emerged as a promising formulation system for poorly water-soluble drugs. Researchers have used various drug compounds over the past two decades to develop SEDDS, and many SEDDS formulations are now available in the market. However, drawbacks such as low drug loading and difficulty in handling and storage have led to the solidification of the SEDDS system by various methods. This review focuses on the spray drying technique as a method of solidification and discusses the advantages, development process, specifications, and characterization of spray-dried S-SEDDS in detail. Additionally, the potential of turning spray-dried SEDDS into tablets by punching to increase bioavailability and stability is also discussed.
CURRENT DRUG DELIVERY
(2023)
Review
Pharmacology & Pharmacy
Gurpreet Singh, Pooja A. Chawla, Abdul Faruk, Viney Chawla, Anmoldeep Kaur
Summary: Biomedical research is focusing on developing new drug delivery systems using molecularly imprinted polymers (MIPs). MIPs are cross-linked polymers with binding sites that match the structure of the target molecules. They have various applications such as purification, biosensing, bioseparation, artificial antibodies, and drug delivery. This article discusses the synthesis and preparation of MIPs, recent advances in drug delivery systems based on MIPs, and their potential for controlled and targeted drug delivery.
CURRENT DRUG DELIVERY
(2023)
Review
Oncology
Indu Passi, Koushal Billowria, Bhupinder Kumar, Pooja A. Chawla
Summary: The article introduces the background of renal cell carcinoma and different types of treatment, focusing on the mechanism of action and side effects of the anti-renal cell carcinoma drug Tivozanib. Tivozanib is a highly selective and potent oral tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs), suitable for the treatment of renal cell carcinoma and can be used in combination with other drugs with minimal side effects. Further research needs to be conducted in multicenter clinical trials.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Organic
Pooja A. Chawla, Simranpreet K. Wahan, Meenakshi Negi, Abdul Faruk, Viney Chawla
Summary: This review showcases the recent advances in the chemistry and biological activities of 4-thiazolidinones. It emphasizes the importance of this molecule in the discovery and development of therapeutics for various diseases. The review also covers synthetic schemes, structure-activity relationships, and patents related to 4-thiazolidinones.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2023)
Review
Chemistry, Organic
Chandrakant Sahu, Abhishek Chaurasiya, Pooja A. Chawla
Summary: This article summarizes the significance of nitrogen-containing heterocyclic compounds in medicinal chemistry and their structure-activity relationship, mechanism and docking studies. The importance of DNA topoisomerase II in anticancer drugs is emphasized, calling for further research on topo II or multi-target topo II inhibitors to overcome drug resistance and reduce toxicity.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Simranpreet K. K. Wahan, Sangeeta Sharma, Pooja A. A. Chawla
Summary: Tuberculosis (TB) is a serious airborne infection caused by Mycobacterium Tuberculosis. It mainly affects the lungs and causes severe symptoms. There is an urgent need to find more effective molecules to combat drug-resistant and inactive TB. Pyrazinamide is currently used as a first-line therapy, but new approaches are required to meet the challenges posed by TB and the rise of drug-resistant strains. The review focuses on the translation of anti-TB activity of pyrazinamide analogues and proposes a novel approach for developing new anti-TB drugs.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Review
Biotechnology & Applied Microbiology
Sumel Ashique, Aakash Upadhyay, Monica Gulati, Dilpreet Singh, Pooja A. Chawla, Viney Chawla
Summary: Nanocomposites have emerged as a promising strategy for drug delivery in the pharmaceutical field, offering numerous benefits and ongoing research development. Polymer nanocomposites (PNCs) are blends of nanomaterials and polymers, where at least one component has a one-dimensional structure and falls within the sub-100 nm range. By incorporating nanoparticles into the polymer matrix, a new class of drug delivery systems with specific characteristics can be created. Nano-clay, a type of nanocomposite, is predominantly utilized for controlled release of therapeutics in various disease conditions. Nanocomposites hold great potential as drug delivery systems due to advantages such as surface and rheological characteristics. Considering their physical and chemical properties, nanocomposites can be categorized into two distinct components. Polymer-fabricated nanocomposites hold potential for use in multi-particulate systems, resulting in controlled drug release profiles with improved mechanical integrity. Nanotechnology-based drug delivery nanocomposites offer benefits including enhanced half-life, greater biocompatibility, reduced immunogenicity, site-specific targeting, and overcoming membrane barriers. Particularly, one-dimensional (1D) nanocomposites exhibit promising potential in theranostics, owing to their increased surface area-to-volume ratios, enabling specific targeting, enhanced encapsulation efficiency, and susceptibility to biomolecules.
CURRENT NANOSCIENCE
(2023)
Review
Chemistry, Medicinal
Parul Grover, Lovekesh Mehta, Anjleena Malhotra, Garima Kapoor, Kandasamy Nagarajan, Parvin Kumar, Viney Chawla, Pooja A. Chawla
Summary: This review provides an overview of the structures and biological activities of three types of Iridoids: iridoid glycosides, non-glycosidic iridoids, and secoiridoids. It also highlights recent research progress in this field and serves as a comprehensive resource for researchers seeking to develop potential compounds for the treatment of various diseases.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Editorial Material
Genetics & Heredity
Nikita Sharma, Debashish D. Das, Pooja A. Chawla
CURRENT GENE THERAPY
(2023)
Review
Chemistry, Organic
Simranpreet K. Wahan, Gaurav Bhargava, Pooja A. Chawla
Summary: Ultrasound is an eco-friendly and cost-effective technique that has attracted interest from chemists for its ability to reduce reaction time and the use of hazardous chemicals, and enhance compound purity. The application of ultrasound waves as a non-polluting energy source has great importance in the field of green and sustainable chemistry. This review focuses on the latest applications of ultrasonication in the preparation of oxygen and nitrogen-containing heterocycles, which play an important role in therapeutically active molecules and will assist new researchers in their ongoing and future research.
CURRENT ORGANIC CHEMISTRY
(2023)
Editorial Material
Pharmacology & Pharmacy
Debashree Debasish Das, Nikita Sharma, Pooja A. Chawla
CURRENT PHARMACEUTICAL ANALYSIS
(2023)
Article
Chemistry, Organic
Simranpreet K. Wahan, Shelly Pathania, Pooja A. Chawla, Gaurav Bhargava
Summary: This study focused on the development of ligand-based pharmacophore and 3D-QSAR models, as well as molecular dynamic simulations, for virtual screening of potential InhA inhibitors. Compound 25 showed promising results and could serve as a potential treatment for drug-resistant tuberculosis.
POLYCYCLIC AROMATIC COMPOUNDS
(2023)
Editorial Material
Chemistry, Organic
Keshav Taruneshwar Jha, Abhimannu Shome, Pooja A. Chawla
Article
Chemistry, Organic
Arshdeep Singh, Anjali Sharma, Pooja A. Chawla
Review
Clinical Neurology
Aniket Saini, Pooja A. Chawla
Summary: ALS is a progressive neurodegenerative disease that primarily affects adults, and the newly approved drug tofersen has emerged as a potential gene therapy to slow down the disease progression by targeting SOD1 mRNA.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
