Medicinal and Environmental Chemistry: Experimental Advances and Simulations (Part I)

Environmental chemistry is an interdisciplinary science with multiple importance in the dynamic lifestyle and consumption pattern. Globally, the environmental regulatory agencies and research institutions feel the extreme need for environmental chemistry for the identification of the nature, source, monitoring, and remediation of pollutants. The pollutants may range from heavy metals, organometallics, polycyclic aromatic hydrocarbons, and nutrients, to the runoff of various other contaminants, their transportation, and interaction with living organisms. Their rapid and accurate separation, identification, quantification using sophisticated techniques, characterization, and understanding of the interactions and mechanisms are the key components of analytical chemistry, for better biochemical or physiological understanding. Contaminants generally have short or long-term toxic implications on the surrounding environment due to direct impact or through bioactivity. Management of environmental pollutants, with minimal impact on biodiversity and human population, is the desired objective of most of the Research & Development programs of International societal relevance. The coordination and effective implementation through sustainable, green, computational technologies may provide the best strategic solutions to the innovators, academicians, and stakeholders, amidst constraints on resources.

Medicinal chemistry is a modern branch of the pioneer subject chemistry. Medicinal chemistry is primarily associated with drug discovery and design in search of New Drug Entities (NDEs). There are different sources, such as natural and synthetic products, animals, marine invertebrates, microorganisms, and recombinant DNA approaches which have been recognized as potential reservoirs for bioactive compounds or drugs. Medicinal chemistry has made several technological innovations, such as computational chemical biology, trial-and-error approach, and bioinformatics, which have greatly improved and accelerated the efficient and competent drug development process. Although with hi-tech innovations in medicinal chemistry, there are several diseases for which treatment is still not available, including the very recent dreadful occurrence of novel coronavirus (COVID-19), which originated from Wuhan city of China. At present, there is no vaccine or drug to cure it. Moreover, the drug development process starting from the identification of a new chemical entity (NCE) to the regulatory approval of NDE is relatively complex, costly, and time-consuming. It can take 10−15 years or even longer to develop and design an NDE. The present chapter intends to discuss and emphasize the different drug sources and drug development processes in medicinal chemistry along with understanding the associated opportunities and challenges.

Estrogens, including estrone, estradiol, and estriol, are the female sex hormones conscientious for the regulation and play a significant role in the developmental process of the feminine reproductive organs. It is used for hypogonadal, postmenopausal, and hormone replacement therapy, as drugs in oral contraceptives and the cure of hormone-dependent cancers, such as breast cancer, ovarian cancer, and prostate cancer, and many other hormone-based complications such as osteoporosis. Environmental xenoestrogens may be classified into two categories- natural (derived from plants or fungi) and synthetic, which include steroidal estrogens, pesticides, and industrial waste. Phytoestrogens are thought to be beneficial for humans, but many environmental pollutants, including pesticides, plastics, and chemicals, which can mimic estrogen compounds, may act like estrogen or could interfere in the mechanism of action of natural estrogens and thus disturb the endocrine processes; such substances are called endocrine disruptors. In the last decade, concentrations of synthetic estrogens have increased rapidly in soil and water worldwide; synthetic xenoestrogens have attracted significant attention. In this chapter, the severe effects of xenoestrogens on human health have been highlighted.

Persistent organic pollutants (POPs) are chemicals compounds that directly affect human and animal health and accumulate in the environment leading to continuous exposure. They have the properties like bioaccumulation, persistence, and biomagnification, which give them the advantage of getting transported by wind and water. POPs were introduced with an intent to benefit the human population, but their excessive usage had made their presence everywhere that turns them to be toxic compounds. Some of the POPs are even generated as a byproduct of chemical and thermal processes. The toxicity evaluation of the POPs moved it towards the class of toxicants that are carcinogenic by nature and imposes a threat to animal and human both. The various analytical approaches had been made to quantify the POPs in various matrices using different sophisticated analytical tools like high-resolution GC-MS and LC-MS/MS. The limit of detection (LOD) and limit of quantification (LOQ) are proposed to be lower as they need to be quantified and detected in biological samples as well.

The risk of adverse health effects of heavy metals, lead (Pb) and cadmium (Cd), was characterized by considering dietary intake of food items and resulting levels of biomarkers, blood Pb levels (PbB), and urinary Cd levels (CdU). Specifically, 35 food items (cereals, pulses, vegetables, and fruits), used in a vegetarian diet in India, were considered. Samples of food items were taken in the winter and autumn seasons and were analysed for Pb and Cd. The observed concentrations were translated into probability density functions (PDF) and Monte Carlo simulation was used to generate levels of chronic daily intake (CDI) that accounted for variability in (i) body weight, (ii) concentration in food and (iii) amount of food intake. The CDI levels were translated into equivalent PDF and the probabilities of exceedance of WHO-suggested provisional tolerable weekly intake of Pb and Cd were estimated. The probability of exceedance of the WHO tolerable limit was 5.55×10-3 for Pb and 7.36×10-4 for Cd. Further, CDIs were translated into PbB levels using a physiologically based pharmacokinetic model. The estimated health risk from (i) ingestion of Pb (i.e., probability of exceedance of safe PbB level of 10 μg/dL) was 9.24×10-3 and (ii) ingestion of Cd (i.e., probability of exceedance of 5 μg/g creatinine) was 4.21×10-5, suggesting that Pb in the environment still poses a substantial risk despite its phasing out from gasoline.

Over the last 50 years, plastics have become an integral part of our day-t- -day life. They seem to be the material of choice, being inexpensive, lightweight, resistant to chemicals, flexible, and mouldable. Over 350 million metric tons of plastics are produced the worldwide and about 50% are discarded within the first year of usage. With plastics being non-biodegradable, their safe disposal is a major challenge. Although one can argue that it is recyclable, its indiscriminate disposal clogs up our rivers, oceans, and land. Some of the chemical components of plastics such as plasticizers, stabilizers, monomers, and colourants are known to leach out from the finished plastics into the stored commodity. They can also be released during various recycling processes. In the present study, undergraduate students were involved in analysing a few representative samples for the estimation of the overall leaching of plastic constituents and heavy metals into food and drinking water. Toxic effects of heavy metals, phthalates and BPA, probable mechanism of toxicity, and some medical strategies have been discussed. Findings from a survey carried out by the students to gauge awareness about leaching in plastics, segregation, and disposal of plastic wastes practised by the community are presented. This experiential learning is aimed at inculcating behavioural change about the judicious usage and proper waste disposal of plastics.

Cancer is a disease characterized by uncontrolled proliferation of cells, and it is caused due to the complex interaction of many cancer-causing factors that change the normal functioning of some genes; these factors may be internal causing mutation, or they may be ecotoxic carcinogens. Ecotoxic carcinogens are the agents that are present in our environment and exposure to them can increase the risk of cancer. These include aflatoxins, arsenic, asbestos, coke-oven emissions, tobacco smoke, wood dust, and indoor emissions from the household combustion of coal, etc. Nature has provided us with an enormous source of natural compounds which have application in various fields such as medicine, cosmetics industry, food, and nutrition, etc. Nature and the natural compounds are serving as a boon to mankind. The medicinal application of natural compounds is one of the most prominent applications of plant products. Plant products have been playing a very important role in the treatment of cancer, as many anticancer drugs have been developed from plant products, such as vinca alkaloids (vinblastine, vincristine, and vindesine), the epipodophyllotoxins (etoposide and teniposide), the taxanes (paclitaxel and docetaxel) and the camptothecin derivatives (camptothecin and irinotecan), etc. The plant-derived anti-cancer drugs have benefits such as easy availability, cost-effectiveness, and fewer side effects. This book chapter will emphasize the various ecotoxic carcinogens and numerous plant-derived anticancer drugs, with their mechanism of action.

In the most basic sense, drug design involves designing molecules that are complementary in shape and charge to the biomolecular target with which they interact, and therefore will bind to it. The therapeutic potential of an organic molecule-based chemotherapeutic candidate is influenced by the basic functional groups, where the stereo-arrangement and stereo-selectivity of groups enhance the therapeutic benefits. Stereo-selective organic molecules in different configurations show diverse activity, such as (R) and (S) enantiomers of ibuprofen are effective pain killers but only (S) naproxen has inflammatory activity. Similarly, the transformation of diethyl stilbesterol has potential estrogenic activity and not the cis form. The softness or hardness of drugs depends on the functionality of organic molecules; mostly, the presence of hydroxyl and carboxylic groups improves the softness. This chapter deals with effective drug designing, including the structure-activity relationship and the influence of various functional groups on the activity of a drug compound. The toxicological impact of drugs on the environment has also been explored. In recent times, it has been successfully studied that residue of drugs could enter the ecosystem through the water channel. It directly or indirectly impacts soil, groundwater, and surface water, and creates environmental and health problems.

This chapter emphasizes the advances in structure-based drug designing to accelerate the drug discovery process. This chapter discusses the various in-silico techniques, such as molecular docking, virtual screening, and molecular dynamics simulations, giving insight into quantum-chemical methods and quantitative structureactivity relationship (QSAR) techniques, which are some of the most popular methods in predicting drug efficiency that helps in designing novel molecular structures. It presents a clear concept of state-of-the-art computational techniques in molecular biology, pharmacology, and molecular medicine, using quantum-chemical techniques. Also, this chapter covers advances in environmental toxicity and its effect on human health. Pharmacological techniques, including pharmacokinetic and pharmacodynamic approaches, have been discussed to predict the effect of drugs on the environment and the human body, including the effects of toxic compounds on the environment and the human body. This chapter will be of immense value to readers of different backgrounds ranging from engineers and scientists to consultants and policymakers. It will be an invaluable resource for students, researchers, and industrial laboratories working in the areas related to medicinal chemistry, cheminformatics, pharmaceutical chemistry, pharmacoinformatic and environmental toxicology.

Chemistry is all around the universe. Green chemistry underpins the enormous social and technological changes in the future. Beginning from eco-friendly chemical synthesis to green catalyst via green chemical reactions, it finds a good correlation with the environment, taking biosynthesis and biomimetic principles into consideration. Widespread interest in this field is seen today among scientists. Considering the present scenario of “The age of tools”, the compatibility with technology today is of utmost importance. Green chemistry is one of the powerful tools to cut the Gordian knot of pollution by reducing chemicals in the surroundings to make them eco-friendly. This chapter emphasizes the various aspects of green chemistry, from its principles to its applications, leading to a sustainable eco-friendly future.