Current Organic Chemistry - Volume 27, Issue 10, 2023

The transition metal-catalyzed C-C and C-X (X=heteroatom) homo and crosscoupling reactions were pioneered as a momentous strategy for the total synthesis of natural products, agrochemicals, pharmaceuticals, etc. Among the various transition metal-catalyzed reactions, manganese catalysis held a distinctive identity owing to its earth-abundance and eco-friendliness apart from its unique characteristics. Despite having many synthetic advancements, exploiting manganese as a catalyst for coupling reactions has recently gained pivotal gravity. An in-depth comprehension of the molecular mechanism of the chemical reaction will provide further insight to optimize the reaction conditions. The mechanisms adopted by Mn-catalyzed couplings are found to differ from other first-row transition metal counterparts. Hence in this article, we provide the state-of-the-art on the detailed theoretical aspects of manganese-catalyzed carbon-carbon (C-C) and carbon-heteroatom (C-X; X=Si) coupling reactions.

Pyridazine derivatives are an important heterocyclic family in medication development. Because of their biological relevance, there has been a surge in interest in the chemistry of pyridazine derivatives in recent years. Anti-tubercular, antifungal, antibacterial, analgesic, anti-inflammatory, antihypertensive, anticancer, antidiabetic, anti-AIDS, cardiovascular activity, anticonvulsant, and possibly useful neuroprotective actions have all been identified for pyridazine derivatives. They have also pesticide and herbicide action. The purpose of this study is to highlight the numerous pyridazine analogs as well as their pharmacological and agricultural implications.

Cancer is becoming more common worldwide, impacting the vast majority of people. As a result, new anticancer drugs are currently being created, and their safety is still being assessed. Pyrazine-based medications are a substantial contribution, as they are one of the most important pharmacophores found in heterocyclic compounds both synthetically and naturally. It's a six-membered aromatic heterocycle with two nitrogen atoms with a wide range of therapeutic applications in drug development and numerous prospects for future enhancement in anticancer drugs by targeting several critical receptors. A number of pyrazine compounds have been shown to inhibit enzymes, receptors, and a range of additional cancer-fighting targets. Researchers are currently focused on the creation of pyrazine-based novel derivatives for cancer treatment in combination with other moieties. As a result, this review illuminates the recent therapeutic expansion of pyrazine-based drugs, as well as their synthetic schemes, tabulated detailed clinical trial drugs, marketed drugs with their primary target, and a list of recently patented and published research papers, all of which will help scientists build successful medications with the appropriate pharmacological activity.

combination of cancer therapy (hyperthermia with other therapies) holds tremendous potential for therapeutic improvement. Conventional methods of inducing hyperthermia are incapable of limiting a high-temperature increase at the tumor location while also preserving unexposed healthy tissues. Different materials available are not suitable for the combined application of hyperthermia and photothermal therapy (PTT). The use of carbonbased nanomaterials for cancer therapy has increased rapidly due to their ability to transport various anticancer drugs and to function as a photothermal agent. In this regard, the graphene family of 2D carbon nanomaterial graphene oxide (GO) and reduced graphene oxide (rGO) has emerged as a promising candidate for cancer PTT due to its excellent photothermal conversion in the near-infrared range, large specific surface area for drug loading, and scope for functionalization with functional groups/ molecules such as photosensitizers, siRNA, ligands, and so on with no cumulative toxicity. The availability of functional groups such as hydroxyls, epoxides, and carbonyls on GO groups, renders flexible modification leading to biocompatibility, facilitating it for an ideal drug delivery vector. In the present review, recent advances in combinational PTT providing synergistic benefits of multiple modalities are discussed.

5-Amino-4-formyl pyrazole 1 was used as a precursor for the synthesis of 6- aminopyrazolo[3,4-b]pyridine-5-carbonitrile 2, and 6-aminopyrazolo[3,4-b]pyridine-5- carboxamides 3 and 4. Pyrazolo[3,4-bpyridines 2, 3, and 4 were treated with different reagents leading to structurally confirmed heterocycles. Mosquito adult females carry and transmit the causatives of many diseases to humans and other domestic animals. Therefore, their management has become a necessity. Ten of the synthesized compounds were tested for larvicidal activity against second-stage C. pipiens larvae. IR spectra were recorded on Shimadzu-408 infrared spectrophotometer. The NMR spectra were performed on a Bruker AV-400 spectrometer and JEOL ECA II 500 MHz. Mass spectrometry was provided on a Varian MAT 312 instrument in EI mode (70 eV). Lethal concentrations were calculated based on probit analysis. Biochemical enzymes were analyzed using analysis of variance ANOVA with Graph Pad Prism 5. Mean comparisons were analyzed using Tukey's test. Five compounds, 1, 2, 4, 5 and 11 exhibited detectable insecticidal activity as these compounds recorded 154.4, 5.6x10³, 8.4, 135.1 and 697.2 ppm, respectively. Moreover, the effect of these insecticidal compounds on lipids and carbohydrates digestive pathways in the larvae was evaluated by comparing the activities of amylase and lipase digestive enzymes in both control and treated larvae. Compounds 1, 4 and 5 showed an inhibitory effect on both lipase and amylase enzymes. Compound 2 inhibited lipase activity, while compound 11 didn’t affect both enzymes compared with the control. Results showed that the incorporation of pyridine and pyrazole induced significant insecticidal activity against larval mosquitoes. Furthermore, insertion of amino or carbonyl groups into the synthesized compounds enhanced the insecticidal activity. Our findings showed that development of such novel compounds is promising in enhancing the agricultural productivity and management of diseases transmitted by insects.

A series of new diethyl 4,6-diarylpyridin-2-yl phosphonate derivatives 3a-f, and 5a,b were synthesized, in good yields, from the reaction of 2-bromo-4,6-diarylpyridines 1a,b with Wittig-Horner reagents 2a-c, and 4 in DMF containing sodium hydride at reflux temperature. The newly synthesized compounds were evaluated for antimicrobial and antioxidant activity. The results demonstrated that compounds 5a and 5b exhibited strong antimicrobial activity against S. aureus, E. faecalis, P. aeruginosa, and S. mutans.Compounds (3d, 3e, 3f) exhibited superior antioxidant scavenging activity with DPPH and ABTS activity with values (85.19 ± 0.33, 80.19 ± 0.98, 82.33 ± 0.90) and (70.11 ± 0.98, 63.55 ± 0.80, 69.54 ± 1.02) at concentrations (2.0 mg.ml^-1), respectively. The results of the molecular docking simulation indicated that the synthesized compounds displayed lower binding energy with various types of interaction at the active sites of Dihydropteroate synthase, Sortase A, LasR, and Penicillin-binding proteins pockets, suggesting that they could have a potential inhibitory effect on the enzymes and exhibit promising antimicrobial properties. Additionally, the simulation of the active sites of the Peroxidase enzyme as an antioxidant receptor revealed that compounds (5a and 5b) exhibited minimal binding energy and a strong affinity for the active pocket of the peroxidase enzyme.

The use of organophosphorus (OP) Nerve Agents (NAs) as chemical weapons still represents a real danger for the safety of population threaten by conflicts or terrorist attacks. A fast and easy-to-use detection of this hazardous gases could make the difference in emergency state. Specifically, the possibility to develop a detection system involving an easily accessible tool, such as a smartphone, is the driving force of the current research work. Due to the great advantages related to the optical sensing, we here report two new BODIPY-based fluorescent receptors for Dimethyl methyl phosphonate (DMMP) NA simulant, with one of the lowest limit of detection. A solid sensor was then developed able to give an OFF/ON response to low ppm concentration of DMMP gas, by using a common smartphone camera with an integrated open-source processing software.

The pursuit of biologically active compounds has led many researchers to synthesize different heterocyclic hybrids with prominent activity. Both coumarin and 1,2,4-triazole are very potent scaffolds whose hybrids have improved biological activities. This study synthesized twenty-one new coumarin-1,2,4-triazole hybrids in a one-step reaction using choline chloride : urea deep eutectic solvent. The green approach to this synthesis has led to shorter reaction times, higher yields, and purity of final compounds. The title compounds were characterized and screened for drug-likeness parameters to evaluate their viability as potential drug candidates and for their in vitro acetylcholinesterase inhibitory activity. All tested compounds complied with the drug-likeness rules. However, they exhibited only weak to moderate inhibitory activity against acetylcholinesterase. Molecular docking analysis revealed that title compounds mostly bind to the peripheral anionic region of the acetylcholinesterase active site, therefore hindering, but not completely obstructing, substrate from entering the enzyme catalytic site.