Anticancer activity and toxicity profiles of 2-benzylidene indanone lead molecule (original) (raw)
Anticancer activity, toxicity and pharmacokinetic profile of an indanone derivative
European Journal of Pharmaceutical Sciences, 2012
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2012
In an attempt to discover a potent and selective anticancer agent, gallic acid has been modified to benzylidene indanones as tubulin polymerization inhibitors. These compounds were evaluated against several human cancer cell lines and also evaluated for inhibition of tubulin polymerase in in vitro assays. Three of the analogues exhibited strong cytotoxicity against human cancer cell lines IC50= 10–880nM and also showed tubulin polymerization inhibition (IC50= 0.62–2.04 μM).
Gallic acid-based indanone derivatives as anticancer agents
Bioorganic & Medicinal Chemistry Letters, 2008
Gallic acid-based indanone derivatives have been synthesised. Some of the indanones showed very good anticancer activity in MTT assay. Compounds 10, 11, 12 and 14 possessed potent anticancer activity against various human cancer cell lines. The most potent indanone (10, IC 50 = 2.2 lM), against MCF-7, that is, hormone-dependent breast cancer cell line, showed no toxicity to human erythrocytes even at higher concentrations (100 lg/ml, 258 lM). While, indanones 11, 12 and 14 showed toxicities to erythrocytes at higher concentrations.
Anti-Cancer Agents in Medicinal Chemistry
Background: Cancer is one of the leading causes of an increasing number of deaths in modern society. As the population increases, there is an increased thrust for screening newer anticancer (phytoconstituents) agents to manage cancers. Around 35000 herbal phytoconstituents are obtained from plants, animals and marine sources to create awareness of green therapy in managing, reducing, and minimizing side effects of modern chemotherapeutics and radiation therapy. The herbal plants are the richest sources of natural remedies and bioactive compounds that promote medicines' alternative systems as a green approach for managing various cancers. The terpenoids, saponins, volatile oils, and flavonoid phytoconstituents are most efficiently used to manage cancer with minimal side effects. Objective: The objectives of the present study are to investigate the efficacious, potent and safe use of herbal phytoconstituents extracts in the management of cancers and study their mechanism of action through alteration of transcription proteins, blocking G-2/M phase, distortion of tubulin structure, generation of reactive oxygen species, lipid peroxidation, cell cycle arrest, and anti-proliferation induced cell apoptosis for target specific cancer treatment. The information was collected from databases such as ScienceDirect, PubMed, Google Scholar, Academia, MedLine, and WoS. Methods: The literature was surveyed, and keywords like cancer therapeutics, metastasis, proliferation, cell apoptosis, cell lines, phytoconstituents for cancer management, and related disorders were screened. Results: The findings suggested that the crude extracts act as an antioxidant, free radical scavenger, or anti-aging agent exploited in the management of cancers along with treatment of other infectious diseases like ulcers, gout, liver diseases, respiratory tract infection, renal disorders, blood disorders, CVD, anti-inflammatory and several wound infections. Conclusion: The phytoactive moieties having herbal extracts help improve the compromised immunity status of affected patients and provide measures for scientific studies of newer anticancer agents in herbal industries.
A new paradigm for the development of anticancer agents from natural products
Journal of experimental therapeutics & oncology, 2006
A novel pharmacology paradigm has been developed which quickly and efficiently moves prospective anticancer drugs from the discovery phase through pharmacology testing and into therapeutic trial assessment. Following discovery, the drug is first assessed in a clonogenic assay which determines the cytotoxic effect of different concentrations of the drug at 3 different exposure durations: 2h, 24h and continuous (168 h). Second, pharmacokinetic information is obtained in both plasma and tumor for the drug administered at the maximum tolerated dose given intravenously. The first study defines the time-concentration profile required to obtain a specific cell survival for the tumor cells; the second study determines the concentration-time profile that can be obtained in both plasma and tumor at the maximum tolerated dose of the drug. The integration of this information determines whether a successful therapeutic trial is possible. Only when a drug shows therapeutic efficacy is a proteomic...
Medicinal Chemistry Research, 2020
Lapachol (1) is a well-studied natural product isolated from plants of the Bignoniaceae family and demonstrates diverse biological effects. Historically, chemical transformation of the lapachol scaffold has yielded new derivatives with impressive biological activity and rich chemical diversity. β-lapachone (2), α-lapachone (3), and 2-acetylfuronaphthoquinone (4) are examples of analogs derived from lapachol that show superior antitumor activity compared with the natural product. In the present study, novel indane carboxylic acid: 2,2-dimethyl-2,3-dihydroindeno[1,2-b]pyran-4,5-dione (9) and methyl 5hydroxy-2,2-dimethyl-2,3,4,5-tetrahydroindeno[1,2-b]pyran-5-carboxylate (10) and naphthoquinone derivatives were synthesized from lapachol with structural similarities to the antitumor lapachol derivatives. The synthesized compounds were evaluated for antiproliferative activities against a panel of human cancer cell lines including in vitro models for neuroblastoma, melanoma, glioblastoma, and non-small cell lung cancer. As expected, the most potent derivatives were those incorporating β-naphthoquinone and α-naphthoquinono[2,3-b]furan skeletons. Many of these compounds possessed nanomolar to single digit micromolar antiproliferative potency. However, the most interesting analog evaluated was the dione 9 with an indeno[1,2-b]pyran skeleton, which demonstrated potent cytotoxic activity. The current investigation identified several new lead compounds that could be used as starting points for anticancer drug discovery.
Plant-based anticancer molecules: A chemical and biological profile of some important leads
Bioorganic & Medicinal Chemistry, 2005
A number of natural products, with diverse chemical structures, have been isolated as anticancer agents. Several potential lead molecules such as camptothecin, vincristine, vinblastine, taxol, podophyllotoxin, combretastatins, etc. have been isolated from plants and many of them have been modified to yield better analogues for activity, toxicity or solubility. Several successful molecules like topotecan, irinotecan, taxotere, etoposide, teniposide, etc. also have emerged as drugs upon modification of these natural leads and many more are yet to come. In this review, the authors have focused on four important anticancer leads, that is, camptothecin, taxol, combretastatin A-4 and podophyllotoxin. Their chemistry, structure and activity relationships, biological activities, modes of action, analogue synthesis and future prospects have been discussed.
Anti-Cancer Constituents from Plants: Mini Review
Dhaka University Journal of Pharmaceutical Sciences
Now-a-days, cancer is a major concern globally, for which a large number of deaths occur annually, instead of the accessibility to various treatment options. Nevertheless, the latest treatment options are principally conglomerate with many side effects. Consequently, the development of an effective and competent anticancer therapy with the lower or minimum adverse or unwanted minor effect is the prime direction of research in the fields of natural product chemistry, drug design, and drug discovery. Phytochemicals available in plants have already been proven as prospective candidates in this regard. In general, phytochemicals are non-selective in their functions and restricted due to their differential activity on cancer cells along with the normal cells. As a consequence, researchers show their interest in isolating bioactive phytochemicals from nature with potent anticancer properties and generate lead compounds based on the natural skeleton of a molecule as a synthetic approach. S...
Anti-Cancer Constituents from Plants: A Brief Review
2020
Now-a-days, cancer is a major concern globally, for which a large number of deaths occur annually, instead of the accessibility to various treatment options. Nevertheless, the latest treatment options are principally conglomerate with many side effects. Consequently, the development of an effective and competent anticancer therapy with the lower or minimum adverse or unwanted minor effect is the prime direction of research in the fields of natural product chemistry, drug design, and drug discovery. Phytochemicals available in plants have already been proven as prospective candidates in this regard. In general, phytochemicals are non-selective in their functions and restricted due to their differential activity on cancer cells along with the normal cells. As a consequence, researchers show their interest in isolating bioactive phytochemicals from nature with potent anticancer properties and generate lead compounds based on the natural skeleton of a molecule as a synthetic approach. S...
Anticancer activity of novel indenopyridine derivatives
Archives of Pharmacal Research, 2012
Eighteen new 4-[2-amino-3-cyano-5-oxo-4-substitutedaryl-4H-indeno[1,2-b]pyridin-1-(5H)-yl]benzenesulfonamide derivatives 6a-q were synthesized via a reaction of aromatic aldehydes, enaminone 3 and malononitrile in one-pot reaction. Also, compounds 6a-q were obtained, via another route by reaction of enaminone 3 with arylidenemalononitriles 4a-q. The structure of the synthesized compounds was characterized by microanalysis, IR, 1 H-NMR, 13 C-NMR and mass spectral data. All the target compounds were subjected to in vitro anticancer activity against breast cancer cell line (MCF7). Compound 6d showed a higher potency with IC 50 value (4.34 µM) than that of the Doxorubicin (5.40 µM), as the reference drug, while compound 6n with IC 50 value (6.84 µM) is nearly as active as Doxorubicin. Also, compounds 6a-c, 6e, 6f, 6h and 6p exhibited a moderate activity, while compounds 3, 6g, 6i-m, 6o and 6q showed weak activity.
Future Journal of Pharmaceutical Sciences
Background Over the years, phytomedicines have been widely used as natural modalities for the treatment and prevention of various diseases by different ethnic groups across the globe. Although, 25% of drugs in the USA contain at least one plant-derived therapeutic compound, currently there is a paucity of plant-derived active medicinal ingredients in the pharmaceutical industry. Scientific evidence-based translation of plant-derived ethnomedicines for their clinical application is an urgent need. The anticancer and associated properties (antioxidative, anti-inflammatory, pro-apoptotic and epithelial-mesenchymal transition (EMT) inhibition) of various plant extracts and phytochemicals have been elucidated earlier. Several of the plant derivatives are already in use under prophylactic/therapeutic settings against cancer and many are being investigated under different phases of clinical trials. Main body The purpose of this study is to systematically comprehend the progress made in the...