Pradip Debnath

Mitochondria are known as the powerhouse of eukaryotic cells. They play a crucial role in several biological processes and maintain cellular health. The ideal condition of mitochondria depends not only on their morphology but also on various micro-environmental factors, including pH, polarity, and temperature. Changes in these factors or malfunctions of mitochondrial species, such as Reactive Oxygen Species (ROS), active nitrogen species, metal cations, anions, and protons, can lead to several diseases in humans, including heart failure, kidney disorders, diabetes, Alzheimer’s disease, and Parkinson's disease. Therefore, monitoring Reactive Small Molecules (RSMs), maintaining micro-environmental factors, and estimating ROS levels in mitochondria are essential for understanding physiological behaviour and the pathogenesis of related diseases. Irregularities in mitochondrial function are closely linked to a range of clinical conditions, highlighting the importance of targeting mitochondria for therapeutic benefits. Over the last decade, numerous studies have focused on the development of small organic conjugated systems for mitochondrial imaging, utilizing optical signal transduction pathways. In this review, the design and synthetic strategies for small organic fluorophores conjugated with a pyridinium acceptor, their applications in mitochondrial imaging, and the detection of RSMs in mitochondria have been discussed. Studies have revealed that small-molecule fluorescent probes are being widely used for the detection and imaging of RSMs located in mitochondria. Moreover, this review covers the mechanistic insights, photophysical properties, biological characteristics of fluorophores, and therapeutic strategies targeting the mitochondria of human cells.

Carbodiimides are unique heterocumulene nitrogenous compounds which are extensively used as efficient precursors in synthetic organic chemistry. They have drawn considerable attention from organic chemists due to their easy availability and unique chemical reactivity. In organic synthesis, they are widely used as intermediates or precursors, especially for the synthesis of nitrogen heterocycles. Recently, many new protocols, including hypervalent iodine-mediated desulfurization of thioureas, I2-catalyzed cross-coupling reactions of isocyanides with amines and transition metal-catalyzed reactions between isocyanides and azides, have been reported for the synthesis of carbodiimides. Although many reviews on carbodiimide chemistry are available in the literature, there is no review focusing on the synthesis of carbodiimides using hypervalent iodine reagents. The present review outlines the hypervalent iodine-mediated synthesis of carbodiimides, covering the literature published from 2008 to 2025. Recent developments in carbodiimide synthesis under catalyst- and oxidant-free conditions, including an electrochemical process, have also been discussed in this review.

We reported here a straightforward strategy for the synthesis of pharmaceutically important 5,6‐dihydropyrimido[4,5‐d]pyrimidines through the reaction between N‐uracil amidines and functionalized aldehydes under catalyst‐free conditions. The condensation reactions between N‐uracil amidines and aldehydes proceeded smoothly in water solvent in the presence of Cs₂CO₃ at 100°C for 15 h under nitrogen atmosphere. A range of aromatic aldehydes bearing electron‐donating as well as electron‐withdrawing groups were well tolerated under optimized reaction conditions and allowed the access of substituted 5,6‐dihydropyrimido[4,5‐d]pyrimidines in 64%–98% yields. The use of a green solvent, an easy work‐up procedure, and a good to excellent yield of products makes this protocol attractive from a sustainable point of view.

Coumarin and its annulated heterocycles are mainly found in natural products, many of which show significant biological activities and are used extensively for the preparation of pharmaceutical products. Investigation revealed that many heterocyclic compounds fused with coumarin moiety exhibited antihelmentic, hypnotic, insecticidal, antifungal, and anti-coagulant properties. In industry, coumarin scaffolds are widely used for the preparation of drugs, agrochemicals, pesticides, and dyes. In recent studies, several coumarin derivatives have been used in materials science for the preparation of organic cell imaging materials, fluorescent biological probes, etc. Due to their immense application potential in biological science and material chemistry, much attention has been paid by researchers towards the synthesis of a new class of coumarin annulated heterocycles. In this paper, the synthesis of coumarin-annulated polycyclic heterocycles via sequential Claisen rearrangement and tin-hydride mediated radical cyclization is reported. The requisite starting materials 3-((4-chlorobut-2-yn-1-yl)oxy)-2H-chromen-2-one (1) was prepared from 3-hydroxycoumarin and 1,4-dichlorobut-2-yne. The Claisen rearrangement of 1 in refluxing chlorobenzene afforded 1-(chloromethyl)pyrano[2,3-c]chromen-5(3H)-one (2). Finally, radical cyclization reactions were carried out smoothly using ⁿBu₃SnH and AIBN in toluene at 110 °C, leading to the coumarin-annulated polycyclic heterocycles in high yields. The process is operationally simple and easy to work-up, making it convenient for the preparation of coumarin annulated heterocycles.

Spiro-oxindoles are important heterocyclic motifs found in various alkaloids, many of which exhibit pharmacological properties. Due to the remarkable biological activity of spiro-oxindoles, significant effort has been made towards the synthesis of substituted spiro-oxindoles. In this paper, preliminary results regarding the synthesis of 3,3′-spiro pentacyclo-oxindole derivatives via the ring-closing metathesis of 3,3-diallyl oxindoles are reported. The ring-closing metathesis reaction proceeded smoothly with Grubb’s catalyst-I (2 mol%) in toluene at room temperature. The desired products, 3,3′-spiro pentacyclo-oxindoles, were obtained in good to excellent yields under standard reaction conditions.

Fused pyrimidines scaffolds such as pyrimidopyrimidines, purines and xanthines are important structural motifs found in various natural products and drug molecules. They are used as anticancer, antiviral, antibacterial, antifungal, antioxidant, antitumor, anti‐diabetic, adenosine potentiating, and hepatoprotective agents. Due to their diverse biological applications, the synthesis of pyrimidopyrimidines, purines and xanthines has gained great importance among the researchers in recent years. Thus, the present study aims to review the synthetic methodologies published during the years 2000–2022 for the preparation of pyrimidopyrimidines, purines and xanthines nucleus. Mechanistic interpretation of some important cases has also been discussed. This survey will help researchers working in the fields of synthetic organic and medicinal chemistry to undertake and improve new approaches for the construction of titled compounds.

The outbreak of SARS-CoV-2 created the biggest crisis to human health and has adversely affected economic growth worldwide. Several vaccines emerged from manufacturers to combat COVID-19. Unfortunately, no therapeutic medication has yet been approved by the FDA for the treatment of this disease. Many researchers have performed in silico studies for the identification of potential SARS-CoV-2 inhibitors from the molecules present in Indian medicinal plants and spices. In this paper, we have performed a structure-based virtual screening (VS) of 120 compounds derived from Nigella sativa (NS) against M^pro, PL^pro, and spike proteins of SARS-CoV-2. Strong binding interactions of M^pro occurred with hits NS-40 and NS-84, whereas hits NS-72D and NS-95D showed strong binding interactions with spike proteins. Interestingly, four promising hits (i.e., NS-21, NS-40, carvacrol (NS_08), and menthol) exhibited good binding interactions with both M^pro and spike proteins. Carvacrol, a monoterpenoid phenol possessing several biological activities, showed a favourable binding affinity towards the papain-like protease of SARS-CoV-2. This small molecule may be used as a natural weapon to combat COVID-19.

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is a big challenge and burning issue to the scientific community and doctors worldwide. Globally, COVID-19 has created a health disaster and adversely affects the economic growth. Although some vaccines have already emerged, no therapeutic medication has yet been approved by FDA for the treatment of COVID-19 patients. Traditionally, we have been using different medicinal plants like neem, tulsi, tea, and many spices like garlic, ginger, turmeric, black seed, onion, etc. for the treatment of flu-like diseases. In this paper, we are highlighting the recent research progress in the identification of natural products from the Indian medicinal plants and spices that have potential inhibition properties against SARS-CoV-2. This study will provide an initiative to stimulate further research by providing useful guidance to the medicinal chemists for designing new protease inhibitors effective against SARS-CoV-2 in future. Graphical Abstract In this review article, recent advances in the identification of natural products from the traditionally used Indian medicinal plants and spices that have potential inhibitory properties against SARS-CoV-2 proteins have been discussed. A prospective natural drug-like compound has minimum side effects. The in vitro study of the reported molecules might be provided a preventive measure against COVID-19 disease. Communicated by Ramaswamy H. Sarma

An efficient and sustainable organocatalyst-catalyzed protocol for the synthesis of structurally diverse pyrimidine fused uracils via the oxidative insertion of alcohols into N-uracil amidines has been developed. With 1.2 equiv. of PhI(OAc)₂ in combination with 10 mol% of TEMPO as the catalyst and Cs₂CO₃ as the base, this protocol has been applied to synthesize a small library of pyrimidine fused uracils in high yields. The PhI(OAc)₂/TEMPO-catalyzed oxidation of alcohol in-situ generated an aldehyde intermediate, which is subsequently reacted with N-uracil amidine to provide the highly functionalized pyrimidine fused uracils. The protocol is operationally simple, and applicable to a broad range of alcoholic substrates, making it highly practical approach for the preparation of pyrimidine fused uracils of biological significance. Graphical Abstract

N-Arylamides are a ubiquitous component of a broad range of natural products and biologically active compounds. In this paper, a new synthetic protocol for the preparation of N-arylamides was developed via the hypervalent iodine-mediated aza-Hofmann-type rearrangement of amidines. The reaction proceeded smoothly at 100 °C in the presence of PhINTs in toluene solvent. The requisite amidine substrates were prepared from amines and nitriles by applying the Pinner reaction approach. Considering the easy access of amidines from nitriles, the overall process is the conversion of nitriles to acetanilide and N-arylamides. As an application of the protocol, the preparation of paracetamol from 4-cyanophenol is also described.