Indoles - A promising scaffold for drug development.

The indole scaffold will continue to play a vital part in the future of drug discovery and agrochemical development. Because of this, the necessity for elegant techniques to enable selective C–H functionalization is vast. Early developments have led to primarily C2 and C3 functionalization because of the inherent reactivity of the pyrrole ring. Despite this, elegant methods have been developed to enable selective C–H functionalization on the benzenoid moiety at C4, C5, C6, and C7. This review focuses on the contributions made in benzenoid C–H functionalization of indoles and other related heteroaromatics such as carbazoles.

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Beyond C2 and C3: Transition-Metal-Catalyzed C–H Functionalization of Indole

Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives.

Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms.

Numerous efficient synthetic methods for enantioselective indole functionalizations have emerged in recent years. This review summarizes the major achievements in the transition-metal-catalyzed enantioselective indole functionalization reactions since 2010 and focuses on C–C bond formation processes, including alkylations, arylations, cycloaddition reactions, and other reactions. It intends to give a compendious overview of the significant progress achieved in this area.

Recent progress in transition-metal-catalyzed enantioselective indole functionalizations.

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Chemia%20heterocyklickych%20zlucenin/Prednaska%202/Doplnkove%20studijne%20materialy/Indole/Biological%20Importance%20of%20the%20Indole%20Nucleus%20in%20Recent%20Years%20-%20A%20Comprehensive%20Review.pdf

Biological importance of the indole nucleus in recent years: A comprehensive review

Heterocyclic compounds are those cyclic compounds in which one or more of the ring carbons are replaced by another atom. The non-carbon atoms in such rings are referred to as ‘‘heteroatoms.’’ Such bicyclic heterocyclic compounds containing pyrrole ring with benzene ring fused to a,b-position are known as Indoles. Indole has a benzene ring and pyrrole ring sharing one double bond. It is a heterocyclic system with 10 electrons from four double bonds and the lone pair from the nitrogen atom. Indole is an important heterocyclic system because it is built into proteins in the form of amino acid tryptophan, because it is the basis of drugs like indomethacin and because it provides the skeleton of indole alkaloids—biologically active compounds from plants including strychnine and LSD. The incorporation of indole nucleus, a biologically accepted pharmacophore in medicinal compounds (Table 1), has made it versatile heterocyclic possessing wide spectrum of biological activities (Table 2). In the present study, we have made an attempt to collect biological properties of imidazole nucleus reported in the new millennium.

Biological Importance of the Indole Nucleus in Recent Years: A Comprehensive Review

The global COVID-19 (coronavirus disease 2019) pandemic, which was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a significant loss of human life around the world. The SARS-CoV-2 has caused significant problems to medical systems and healthcare facilities due to its unexpected global expansion. Despite all of the efforts, developing effective treatments, diagnostic techniques, and vaccinations for this unique virus is a top priority and takes a long time. However, the foremost step in vaccine development is to identify possible antigens for a vaccine. The traditional method was time taking, but after the breakthrough technology of reverse vaccinology (RV) was introduced in 2000, it drastically lowers the time needed to detect antigens ranging from 5–15 years to 1–2 years. The different RV tools work based on machine learning (ML) and artificial intelligence (AI). Models based on AI and ML have shown promising solutions in accelerating the discovery and optimization of new antivirals or effective vaccine candidates. In the present scenario, AI has been extensively used for drug and vaccine research against SARS-COV-2 therapy discovery. This is more useful for the identification of potential existing drugs with inhibitory human coronavirus by using different datasets. The AI tools and computational approaches have led to speedy research and the development of a vaccine to fight against the coronavirus. Therefore, this paper suggests the role of artificial intelligence in the field of clinical trials of vaccines and clinical practices using different tools.

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Artificial Intelligence-Based Data-Driven Strategy to Accelerate Research, Development, and Clinical Trials of COVID Vaccine

Background Depression is a psychiatric disorder leading to anhedonia and lack of interest and motivation. Depressive symptoms are triggered by stressful life events, and patients with major depression are at significantly increased risk of attempting suicide. The crucial concern in depression treatment with antidepressant medications is that few weeks are required to show the therapeutic effect along with moderate side effects. The use of herbal medications is a new strategy for the treatment of depression which is often based on medicinal plants.Aegle marmelos (L.) Corr. (family: Rutaceae) is reported to have several actions on the central nervous system producing beneficial effects in anxiety, Alzheimer's disease, Parkinson's disease, epilepsy, and convulsion. Thus, the current investigation designed to assess the antidepressant activity of the standardized hydroethanolic extract of Aegle marmelos (EAM) leaves in male rats exposed to the chronic unpredictable mild stress (CUMS) paradigm. Methods Rats were divided in 5 groups. The control group was not subjected to experimental CUMS paradigm, while 4 other groups were subjected to CUMS paradigm to induce depression-like behaviour from day 1 to day 28. Following the CUMS paradigm, 4 groups were divided as CUMS disease control, CUMS+EAM (150 mg/kg, p.o.), CUMS+EAM (300 mg/kg, p.o.), and CUMS+imipramine (15 mg/kg, p.o.), and treatment was given for seven consecutive days to the respective groups (day 29 to day 35). Behavioural parameters such as open field test, forced swim test, sucrose feeding test, and tail suspension test on day 1, day 28, and day 35 were measured, and biochemical parameters such as plasma corticosterone level, serotonergic system (5-HT, 5-HIAA, and 5-HT/5-HIAA), mitochondrial function, and proinflammatory mediators (TNF-α, IL-1β, and IL-6) were estimated in hippocampus (HIP) and prefrontal cortex (PFC) regions of the brain on day 35, after the behavioural observations. On the other hand, phytochemical profile of Aegle marmelos was done. Results On day 35, EAM (300 mg/kg) significantly reduced the immobility time during the tail suspension test from 208.66 ± 4.72 s to 108.83 ± 4.81 s and forced swim test from 200.16 ± 4.12 s to 148.5 ± 4.58 s. It also enhanced the behavioural parameters in the open field test such as ambulation from 26.5 ± 2.14 to 56.5 ± 1.80, rearing from 8.33 ± 0.71 to 19 ± 0.57, time spent in centre from 9.16 ± 0.9 to 17.16 ± 0.79 s, total distance travelled from 2.36 ± 0.12 to 4.68 ± 0.10 m, and anhedonia in the sucrose feeding test from 109.33 ± 1.08 to 135.83 ± 3.91 mL. The stimulation of the HPA axis resulting elevated corticosterone level caused by CUMS was reduced by EAM (300 mg/kg) from 80.12 ± 2.020 to 48.25 ± 2.407 μg/dL. Furthermore, EAM (300 mg/kg) increase CUMS-induced changes in serotonin (5-HT) level in HIP and PFC from 3.132 ± 0.09586 to 4.518 ± 0.1812 and 4.308 ± 0.1593 to 5.262 ± 0.1014 ng/mg protein, respectively. EAM (300 mg/kg) significantly attenuated the CUMS-induced changes in proinflammatory cytokine production and mitochondrial function in HIP and PFC. One group used to determine the acute toxicity as per OECD-23 standard protocol which resulted that 300 mg/kg EAM has no significant acute toxicity. Total phenolic content and total flavonoid content of standardized hydroalcoholic extract of AM was found 95.024 ± 2.431 and 36.820 ± 3.41, respectively, and additional identification tests showed the presence of alkaloids, tannins, saponins, cardiac glycosides, flavonoids, and terpenoids. Conclusion On the basis of findings, EAM can be inferred as a potential antidepressant-like effect of this plan in preclinical research.

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Antidepressive-Like Effect of Aegle marmelos Leaf Extract in Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviour in Rats

Background; 1,5-benzothiazepine moiety is a very important pharmacophore bioactive compound that exhibits different biological activities. By the literature review the basic structure requirements for anticonvulsant activity contains molecular weight less than 500, Oil/water distribution coefficient is less than 5, Hydrogen bond donors more than 5 and Hydrogen bond acceptor more than 10. Aim of study: Aim of the study is to synthesize a novel series of 1,5-benzothiazepine nucleus containing Mannich bases which retained anticonvulsant biological activities with less toxic effect. Materials & methods: We synthesized successfully various substituted 3-(Dimethyl/Diethylamino)-{1-[4-Methyl-2 substitutedphenyl-2,5-dihydro-1,5 benzothiazepin-3-yl]}propan-1-one (6a-6t). Completion of chemical reaction was monitored by thin layer chromatography on silica gel G coated plates and final compounds were purified by recrystallisation with methanol. The chemical structure of synthesized compounds confirmed by chromatographi, electro analytical and physiochemical analysis. Results & discussion: All the novel synthesized compounds screened by anticonvulsant activity by maximum electroshock induced seizure against Phenytoin as standard. All the synthesized compounds showed significant anticonvulsant activity. The most potent significant compound was found 3-(Dimethylamino)-{1-[3-chlorophenyl-4-methyl-2, 5-dihydro-1,5-benzothiazepin-3-yl]}propan-1-one (6e). Further, preliminary safety profile of most potent significant compound 6e was evaluated by acute oral toxicity and neurotoxicity testing.

Synthesis, preliminary anticonvulsant and toxicity screening of substituted 3-(Dimethyl/Diethylamino)-{1-[4-methyl-2-substitutedphenyl-2,5-dihydro-1,5-benzothiazepin-3-yl]}propan-1-one

Devender Pathak

Papers

Biological importance of the indole nucleus in recent years: A comprehensive review

Biological Importance of the Indole Nucleus in Recent Years: A Comprehensive Review

Artificial Intelligence-Based Data-Driven Strategy to Accelerate Research, Development, and Clinical Trials of COVID Vaccine

Antidepressive-Like Effect of Aegle marmelos Leaf Extract in Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviour in Rats

Synthesis, preliminary anticonvulsant and toxicity screening of substituted 3-(Dimethyl/Diethylamino)-{1-[4-methyl-2-substitutedphenyl-2,5-dihydro-1,5-benzothiazepin-3-yl]}propan-1-one