Allostery Illuminated: Harnessing AI and Machine Learning for Drug Discovery.

In the past several years there has been rapid adoption of artificial intelligence (AI) and machine learning (ML) tools for drug discovery. In this Microperspective, we comment on recent AI/ML applications to the discovery of allosteric modulators, focusing on breakthroughs with AlphaFold, structure-based drug discovery (SBDD), and medicinal chemistry applications. We discuss how these technologies are facilitating drug discovery and the remaining challenges to identify allosteric binding sites and ligands.

Empowering Voices: Inspiring Women in Medicinal Chemistry.

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists. The responses and contributions highlight their passions and motivations, such as their love of the sciences and their drive to improve human health by contributing to basic research and creating lifesaving drugs.

Empowering Voices: Inspiring Women in Medicinal Chemistry.

As we celebrate International Women's Day 2024 with the theme "Inspire Inclusion", the women of the ACS Medicinal Chemistry Division (MEDI) want to foster a sense of belonging, relevance, and empowerment by sharing uplifting stories of what inspired them to become medicinal chemists. In this editorial, we are featuring female medicinal chemistry scientists to provide role models, encouragement, and inspiration to others. We asked women medicinal chemists to contribute a brief paragraph about what inspired them to become medicinal chemists or what inspires them today as medicinal chemists. The responses and contributions highlight their passions and motivations, such as their love of the sciences and their drive to improve human health by contributing to basic research and creating lifesaving drugs.

Morphological performance and seasonal pattern of water relations and gas exchange in Pistacia lentiscus plants subjected to salinity and water deficit.

Soil water deficit and salinity represent a major factor impacting plant survival and agricultural production. The frequency and severity of both abiotic stresses are expected to increase in a context of climate change, especially in arid and semi-arid regions. This work studied the growth pattern, biomass and mineral distribution and the seasonal pattern of water status, photosynthetic rate and stomatal conductance in plant of Pistacia lentiscus grown under different levels of water deficit and salinity. P. lentiscus plants growing under greenhouse conditions were subjected to four irrigation treatments during 11 months: control (C, 1 dS m-1), moderate water deficit (MW, 1dS m-1, 60% of the control), severe water deficit (SW, 1 dS m-1, 40% of the control) and saline (S, 4dS m-1). The results show that Pistacia lentiscus plants were more affected by deficit irrigation than salinity. Deficit irrigation and salinity inhibited plant height, with reductions of 20%, 22% and 35% for S, MW and SW, respectively. Total leaf area was not modified by effect of the treatments, with the result that plant compactness increased in MW. The salt stressed plants only showed lower relative growth rate at the end of the experiment. Plants responded to saline or drought stress by increasing their osmotic adjustment, which was more pronounced under salinity. Saline plants had the highest values in Na+ and Cl- ions and the lowest values for K+/Na+ and Ca2+/Na+ ratios in leaves and stems, which is correlated with a decrease in growth, stomatal conductance, photosynthesis and stem water potential, and can be used as a diagnostic tool to assess plant tolerance to salinity stress. As a measure of plant hydration, relative water content was more sensitive to deficit irrigation than salinity, being a good indicator of water stress. P. lentiscus plants subjected to both deficit irrigation treatments exhibited an increase in their intrinsic water use efficiency, which is an important adaptation for plants growing in environments with water scarcity.

Excellence in Medicinal Chemistry: Celebrating ACS Medicinal Chemistry Division (MEDI) Awards. A Call for Nominations.

The American Chemical Society Division of Medicinal Chemistry (MEDI) confers a range of awards, fellowships and honors to recognize excellence in medicinal chemistry. To celebrate the creation of the Gertrude Elion Medical Chemistry Award the ACS MEDI Division wishes to take this opportunity to inform the community of the many awards, fellowships and travel grants that are available for members.

Accelerating Drug Discovery: Synthesis of Complex Chemotypes via Multicomponent Reactions.

The generation of multiple bonds in one reaction step has attracted massive interest in drug discovery and development. Multicomponent reactions (MCRs) offer the advantage of combining three or more reagents in a one-pot fashion to effectively yield a synthetic product. This approach significantly accelerates the synthesis of relevant compounds for biological testing. However, there is a perception that this methodology will only produce simple chemical scaffolds with limited use in medicinal chemistry. In this Microperspective, we want to highlight the value of MCRs toward the synthesis of complex molecules characterized by the presence of quaternary and chiral centers. This paper will cover specific examples showing the impact of this technology toward the discovery of clinical compounds and recent breakthroughs to expand the scope of the reactions toward topologically rich molecular chemotypes.

Enhancing the Visibility of Women in the ACS Division of Medicinal Chemistry (ACS MEDI).

On the occasion of the 2023 International Women's Day on March 8, 2023, we want to celebrate and highlight the contributions of many women volunteers in the American Chemical Society Division of Medicinal Chemistry (ACS MEDI).

Enhancing the Visibility of Women in the ACS Division of Medicinal Chemistry (ACS MEDI).

On the occasion of the 2023 International Women's Day on March 8, 2023, we want to celebrate and highlight the contributions of many women volunteers in the American Chemical Society Division of Medicinal Chemistry (ACS MEDI).

Collaboration and knowledge integration for successful brain therapeutics - lessons learned from the pandemic.

Brain diseases are a major cause of death and disability worldwide and contribute significantly to years of potential life lost. Although there have been considerable advances in biological mechanisms associated with brain disorders as well as drug discovery paradigms in recent years, these have not been sufficiently translated into effective treatments. This Special Article expands on Keystone Symposia's pre- and post-pandemic panel discussions on translational neuroscience research. In the article, we discuss how lessons learned from the COVID-19 pandemic can catalyze critical progress in translational research, with efficient collaboration bridging the gap between basic discovery and clinical application. To achieve this, we must place patients at the center of the research paradigm. Furthermore, we need commitment from all collaborators to jointly mitigate the risk associated with the research process. This will require support from investors, the public sector and pharmaceutical companies to translate disease mechanisms into world-class drugs. We also discuss the role of scientific publishing in supporting these models of open innovation. Open science journals can now function as hubs to accelerate progress from discovery to treatments, in neuroscience in particular, making this process less tortuous by bringing scientists together and enabling them to exchange data, tools and knowledge effectively. As stakeholders from a broad range of scientific professions, we feel an urgency to advance brain disease therapies and encourage readers to work together in tackling this challenge.

Acute and Rapid Response of Melissa officinalis and Mentha spicata to Saline Reclaimed Water in Terms of Water Relations, Hormones, Amino Acids and Plant Oxylipins.

The use of reclaimed water is considered an efficient tool for agricultural irrigation; however, the high salinity associated to this water could compromise plant quality and yields. Balm and spearmint plants were submitted for 15 days to three irrigation treatments in a controlled chamber: control with EC: 1.2 dS m-1 (control), reclaimed water from secondary effluent (EC: 1.6 dS m-1) (S) and water from secondary effluent with brine (EC: 4.4 dS m-1) (SB). The plant water status, stomatal and hormonal regulation, nutritional response, concentration of amino acids and plant oxidative stress-based markers, as well as growth were evaluated. Both species irrigated with saline reclaimed water reduced leaf water potential and gas exchange in comparison with control plants, following 2 days of exposure to irrigation treatments. Nevertheless, spearmint plants recovered photosynthetic activity from the seventh day onwards, maintaining growth. This was attributed to hormonal changes and a greater accumulation of some amino acids and some plant oxylipins (phytoprostanes) in comparison to balm plants, which contributed to the improvement in the organoleptic and health-promoting properties of spearmint. A longer irrigation period with saline reclaimed water would be necessary to assess whether the quality of both species, especially spearmint, could further improve without compromising their growth.