A QSAR study on the cytotoxicity of podophyllotoxin analogues against various cancer cell lines.

The powerful inhibitory activity of podophyllotoxin (a natural product) on cell growth led to the development of clinically useful anticancer agents such as etoposide, teniposide, and etopophos. Although, these podophyllotoxin derivatives show good clinical effects against various cancers, its use often results in various undesired side effects, drug resistance, and cytotoxicity towards the normal cells. In order to overcome these limitations, it is essential to search new podophyllotoxin analogues with improved anticancer activity and fewer side effects to gain the maximum benefits for the cancer patients.

QSAR modeling of taxane analogues against colon cancer.

Although taxanes such as paclitaxel and docetaxel are the two most important clinically available anticancer drugs for the treatment of various cancers (including colon cancer), the success of these two drugs has been tempered by the development of various unbearable side effects as well as multi-drug resistance. Therefore, it is essential to search new taxane analogues with improved anticancer activity and fewer side effects to gain the maximum benefits for colon cancer patients. In this paper, four series of taxane derivatives were used to correlate their inhibitory activities against colon cancers mainly with the hydrophobic and steric descriptors of their substituents in order to gain a better understanding of their chemical-biological interactions.

Taxane analogues against lung cancer: a quantitative structure-activity relationship study.

Lung cancer is the second most common cancer in both men (after prostate cancer) and women (after breast cancer). The microtubule-stabilizing taxane such as docetaxel is the only agent currently approved for both first- and second-line treatment of advanced non-small cell lung cancer. Although docetaxel has made significant progress in the treatment of lung cancers either using alone or in combination with various novel targeted agents, its use often results in various undesired side-effects.

Overcoming tumor drug resistance with C2-modified 10-deacetyl-7-propionyl cephalomannines: a QSAR study.

The microtubule-stabilizing taxanes such as paclitaxel and docetaxel are the two most important anticancer drugs currently used in clinics for the treatment of various types of cancers. However, the major common drawbacks of these two drugs are drug resistance, neurotoxicity, substrate for drug transporter P-gp, cross-resistance with other chemotherapeutic agents, low oral bioavailability, and no penetration in the blood-brain barrier (BBB). These limitations have led to the search for new taxane derivatives with improved biological activity.

Combating the threat of anthrax: a quantitative structure-activity relationship approach.

Bacterial agents or products more likely to be used as biological weapons of mass destruction are Bacillus anthracis, Francisella tularensis, Yersinia pestis, and the neurotoxin of Clostridium botulinum. Anthrax is an acute infectious disease with a high mortality rate caused by Bacillus anthracis, reinforcing the need for better adjunctive therapy and prevention strategies. In this paper, we developed 7 QSAR models on penicillin-based inhibitors of the class A and B beta-lactamases from B.

A QSAR study for the cytotoxic activities of taxoids against macrophage (MPhi)-like cells.

A series of taxoids (modified at the C-3'N position) have been used for the development of two QSAR models for their cytotoxic activities against macrophage (MPhi)-like cells J774.1 and J7.DEF3.

Larvicidal activities of some organotin compounds on mosquito larvae: a QSAR study.

Mosquitoes are not only the cause of nuisance by their bites but also transmit deadly diseases like malaria, filariasis, yellow fever, dengue, and Japanese encephalitis. In this paper, nine QSAR models were developed using different series of organotins with respect to their larvicidal activities against Aedes aegypti and Anopheles stephensi mosquito larvae. Internal [cross-validation (LOO-q(2)), quality factor (Q), Fischer statistics (F), and Y-randomization] and external validation tests have validated all these QSAR models.

Taxane analogues against breast cancer: a quantitative structure-activity relationship study.

Breast cancer is the second leading cause of cancer death among women in the United States. Two taxane analogues, taxol and taxotere, are the most important antimitotic drugs currently in clinical use for the treatment of breast cancers. However, recent reports have indicated that the use of these drugs often results in various undesired side effects as well as multi-drug resistance.

Understanding tubulin/microtubule-taxane interactions: a quantitative structure-activity relationship study.

For years, the microtubule-stabilizing agents paclitaxel and docetaxel (progenitors of the family of taxanes) have been the most successful anticancer drugs currently used in clinics. However, both drugs are associated with notorious side effects, drug resistance, and cross resistance with other chemotherapeutic agents. These limitations have led to the search for new drugs with improved biological activity.

20-(S)-camptothecin analogues as DNA topoisomerase I inhibitors: a QSAR study.

The interest in the application of the quantitative structure-activity relationships (QSAR) has steadily increased in recent decades because it has repeatedly proven itself to be a low-cost, high-return investment. Potential use of QSAR models for screening of chemical databases or virtual libraries before their synthesis appears equally attractive to chemical manufacturers, pharmaceutical companies, and government agencies. We hope it may also be useful in the design and development of new camptothecin derivatives as DNA topoisomerase I (topo I) inhibitors.

Investigation of DNA-binding properties of organic molecules using quantitative structure-activity relationship (QSAR) models.

Due to the great potential of DNA as a receptor, many classes of synthetic and naturally occurring molecules exert their anticancer activities through DNA-binding. In the field of antitumor DNA-binding agents, a number of acridine and anthracycline derivatives are in the market as chemotherapeutic agents. However, the clinical application of such classes of compounds has encountered problems such as multi-drug resistance and secondary and/or collateral effects.

Matrix metalloproteinases (MMPs): chemical-biological functions and (Q)SARs.

Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc-containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan. They are regulated by hormones, growth factors, and cytokines, and are involved in ovarian functions. MMPs are excreted by a variety of connective tissue and pro-inflammatory cells including fibroblasts, osteoblasts, endothelial cells, macrophages, neutrophils, and lymphocytes.

Comparative QSAR studies on PAMPA/modified PAMPA for high throughput profiling of drug absorption potential with respect to Caco-2 cells and human intestinal absorption.

Despite the dramatic increase in speed of synthesis and biological evaluation of new chemical entities, the number of compounds that survive the rigorous processes associated with drug development is low. Thus, an increased emphasis on thorough ADMET (absorption, distribution, metabolism, excretion and toxicity) studies based on in vitro and in silico approaches allows for early evaluation of new drugs in the development phase. Artificial membrane permeability measurements afford a high throughput, relatively low cost but labor intensive alternative for in vitro determination of drug absorption potential; parallel artificial membrane permeability assays have been extensively utilized to determine drug absorption potentials.

Understanding human rhinovirus infections in terms of QSAR.

The human rhinoviruses (HRVs) are the single most important cause of common colds. The widespread nature of this affliction, the economic consequences, and the well-known impracticality of vaccine development due to the large number of HRV serotypes (>100) have justified the search for chemotherapeutic agents. The interest in the application of quantitative structure-activity relationships has steadily increased in recent decades and we hope it may be useful in the search for anti-HRV agents.

Cytotoxicity of organic compounds against ovarian cancer cells: a quantitative structure-activity relationship study.

The interest in the application of structure-activity relationships has steadily increased in recent decades. In the present paper, we have discussed the cytotoxicity of various sets of organic compounds against ovarian cancer cells by the formulation of a total number of 11 QSARs. Hydrophobicity is found to be one of the most important determinants of activity followed by steric parameters.

Utility of the mouse dermal promotion assay in comparing the tumorigenic potential of cigarette mainstream smoke.

The International Agency for Research on Cancer (IARC) has classified a number of the chemical constituents reported in cigarette mainstream smoke (MS) as carcinogens. In the international literature, 81 IARC classified carcinogens have been reported historically in MS. Cigarette smoke is a complex aerosol of minute liquid droplets (termed the particulate phase) suspended within a mixture of gases (CO(2), CO, NO(x), etc.

Chemical Toxicity on HeLa Cells.

HeLa cells were named for Henrietta Lacks, who died in 1952 from an infection of a special type of cancer. Margaret Gey, her physician, started working with these cancer cells that are still used for medical research. In the present review, an attempt has been made to collect the data for the effects of different chemicals on HeLa cells and to discuss them by the formulation of a total number of 22 QSAR.

A QSAR study on influenza neuraminidase inhibitors.

Influenza is a major respiratory infection associated with significant morbidity in the general population and mortality in elderly and high-risk patients. It is an RNA virus that contains two major surface glycoproteins, neuraminidase and hemagglutinin. These proteins are essential for infection.

A QSAR review on melanoma toxicity.

Melanoma is one of the most aggressive forms of skin cancer and is currently attracting our attention particularly in the area of quantitative structure-activity relationships (QSAR). In the present review, an attempt has been made to collect the data for different sets of compounds and to discuss their toxicities toward melanoma cells by the formulation of a total number of 36 QSAR.

An approach toward the problem of outliers in QSAR.

Compounds that have unexpected biological activity and are unable to fit in a QSAR model are known as outliers. These are valuable in defining the limitations under which compounds act by a common molecular mechanism modeled by one or more descriptors, and also in defining the experimental limitations of the biological test data. Thus, the outliers should be submitted to particular attention to see if the reason for their peculiarity can be determined.

The role of hydrophobic properties of chemicals in promoting allosteric reactions.

An allosteric reaction has been found in a variety of instances where an inverted parabolic relationship between biological activity and hydrophobicity is apparent, that is the activity first decreases as hydrophobicity increases and after a certain point, activity begins to increase. This could be attributed to the ligands causing a change in the receptor structure. In this report, the role of hydrophobic properties of chemicals in promoting allosteric reactions have been discussed in term of hydrophobicity (logP) by the formulation of a total number of 50 QSAR equations.