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Type 2 Diabetes Mellitus (T2DM) is known to be associated with an increase in total plasma free fatty acid (FFA) concentration. The present study was conducted to determine the changes in plasma fatty acids at different levels of glycation in type 2 diabetes mellitus. The study involved 50 subjects having different levels of glycation (HbA1c 4.9–15.0%) and further categorized in 5 groups [group 1 (HbA1c <6%), group 2 (HbA1c 6–7%), group 3 (HbA1c 7.1–9%), group 4 (HbA1c (9.1–12%) and group 5 (HbA1c >12%)] with 10 subjects in each group. A total of 19 free fatty acids were detected by gas chromatography-mass spectrometry (GC-MS) analysis in the plasma samples. The levels of lauric acid (C12:0) and stearic acid (C18:0) were significantly raised at an advanced stage of glycation (HbA1c 9.1–15%). Long-chain fatty acids, pentadecanoic acid (C15:0) and palmitic acid (C16:0) levels were elevated in hyperglycemia as compared to normoglycaemic subjects (HbA1c <6%). Moreover, levels of mono and polyunsaturated fatty acids, oleic acid (C18:1) and linoleic acid (C18:2, w6) were significantly decreased in patients with increased levels of glycation (HbA1c 6–15%). Conclusion : GC-MS is a novel way to study the plasma fatty acid profiling and findings of this study suggest that monitoring alterations in plasma FFA profile may be of prognostic value. Image 1 • Fatty acid profiling was carried out at different glycation levels in human subjects. • Palmitic acid (C16:0) level was significantly elevated in type 2 diabetes mellitus (T2DM) patients. • Stearic acid (C18:0) and margaric acid (C17:0) were positively and negatively correlated with HbA1c, respectively. • Mono and polyunsaturated fatty acid levels were significantly decreased in T2DM patients. [ABSTRACT FROM AUTHOR]

Abstract Piperidine is an important pharmacophore, a privileged scaffold and an excellent heterocyclic system in the field of drug discovery which provides numerous opportunities in studying/exploring this moiety as an anticancer agent by acting on various receptors of utmost importance. Cancer is an uncontrolled division of cells that results in the formation of tumour which have the potential to migrate to other parts of the body (metastasis) finally becoming a major threat to human population. Since piperidine displayed great potential in this area it is being further probed to get novel entities for the treatment of cancer. This review throws light on recent biological expansions of piperidine along with structure activity relationships to deliver association between various synthesized newer/novel derivatives and receptor sites. Graphical abstract Image 1 Highlights • Piperidine is a six membered heterocyclic moiety which comprises of five methylene groups (-CH 2 -) & one amine group (-NH-). • Piperidine has an excellent anticancer profile. • Analysis of structure activity relationships of piperidine derivatives will help in designing newer anticancer agents. [ABSTRACT FROM AUTHOR]

Abstract Pyrrole is a heterocyclic ring template with multiple pharmacophores that provides a way for the generation of library of enormous lead molecules. Owing to its vast pharmacological profile, pyrrole and its analogues have drawn much attention of the researchers/chemists round the globe to be explored exhaustively for the benefit of mankind. This review focusses on recent advancements; pertaining to pyrrole scaffold, discussing various aspects of structure activity relationship and its bioactivities. Graphical abstract Image 1 Highlights • Pyrrole is a heterocyclic aromatic five membered multiple pharmacophoric template. • The name pyrrole came from the Greek word 'pyrrols' means fiery from the reaction. • Pyrroles exhibit lower basicity due to delocalization of lone pair of electrons of nitrogen atom in the pyrrole ring. • The NH and CH protons are moderately acidic and can be deprotonated with strong bases, showing its nucleophilic nature. [ABSTRACT FROM AUTHOR]

Abstract: A number of 5-(4-substituted phenyl)-2-(substituted benzylsulfanyl)-4-(substituted phenyl)-6-methyl-1,4-dihydro-5-pyrimidine carboxamides (1–30) were designed and synthesized keeping in view the structural requirements as suggested in the pharmacophore model for antihypertensive activity. All the synthesized compounds were tested for antihypertensive activity by non-invasive blood pressure (NIBP) measurements (tail-cuff method) in rats. Almost all the tested compounds displayed considerable decrease in the blood pressure as compared to control. Thirteen compounds showed significant antihypertensive activity comparable to the standard drug nifedipine. [ABSTRACT FROM AUTHOR]

Abstract: A number of N-(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones (4a–t) were synthesized and tested for their anticonvulsant activity against the two seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out. [Copyright &y& Elsevier]

• Convulsion is a neurological condition triggered by recurring unprovoked seizure that may upset physical, mental and behavioural operations. • SAR and docking studies of newer anti-epileptic agents have been explained. • Novel anti-epileptic agents have been established with an improved safety, potency and efficacy. Although there have been many advancements in scientific research and development, the cause of epilepsy still remains an open challenge. In spite of high throughput research in the field of anti-epileptic drugs, efficacy void is still prevalent before the researchers. Researchers have persistently been exploring all the possibilities to curb undesirable side effects of the anti-epileptic drugs or looking for a more substantial approach to diminish or cure epilepsy. The drug development has shown a hope to medicinal chemists and researchers to carry further research by going through a substantial literature survey. This review article attempts to describe the recent developments in the anti-epileptic agents, pertaining to different molecular scaffolds considering their structure-activity relationship, docking studies and their mechanism of actions. Image, graphical abstract [ABSTRACT FROM AUTHOR]

In our earlier study, we have reported that a phenolic compound 2-hydroxy-4-methoxybenzaldehyde from Janakia arayalpatra root extract was active against Viper and Cobra envenomations. Based on the structure of this natural product, libraries of synthetic structurally variant phenolic compounds were studied through molecular docking on the venom protein. To validate the activity of eight selected compounds, we have tested them in in vivo and in vitro models. The compound 21 ( 2-hydroxy-3-methoxy benzaldehyde), 22 (2-hydroxy-4-methoxybenzaldehyde) and 35 (2-hydroxy-3-methoxybenzylalcohol) were found to be active against venom-induced pathophysiological changes. The compounds 20 , 15 and 35 displayed maximum anti-hemorrhagic, anti-lethal and PLA 2 inhibitory activity respectively. In terms of SAR, the presence of a formyl group in conjunction with a phenolic group was seen as a significant contributor towards increasing the antivenom activity. The above observations confirmed the anti-venom activity of the phenolic compounds which needs to be further investigated for the development of new anti-snake venom leads. [ABSTRACT FROM AUTHOR]

The over expression of EGFR has been recognized as the driver mechanism in the occurrence and progression of carcinomas such as lung cancer, breast cancer, pancreatic cancer, etcetera. EGFR receptor was thus established as an important target for the management of solid tumors. The occurrence of resistance caused as a result of mutations in EGFR has presented a formidable challenge in the discovery of novel inhibitors of EGFR. This has resulted in the development of three generations of EGFR TKIs. Newer mutations like C797S cause failure of Osimertinib and other EGFR TKIs belonging to the third-generation caused by the development of resistance. In this review, we have summarized the work done in the last five years to overcome the limitations of currently marketed drugs, giving structural activity relationships of quinazoline-based lead compounds synthesized and tested recently. We have also highlighted the shortcomings of the currently used approaches and have provided guidance for circumventing these limitations. Our review would help medicinal chemists streamline and guide their efforts towards developing novel quinazoline-based EGFR inhibitors. Image 1 • Six quinazoline-based EGFR TKIs are in market for treatment of 10–30% of NSCLC cases. • Current limitations like acquired resistance hinder effective use of available drugs. • Last 5 years-synthesis of new quinazoline leads to overcome the existing challenges. • Next decade-focus on designing drugs targeting EGFR harboring tertiary mutations. • Focus would also be on combination approach targeting multiple pathways to treat cancer. [ABSTRACT FROM AUTHOR]

Thiazolidinedione is an important heterocyclic ring system, a pharmacophore and a privileged scaffold in medicinal chemistry; is a derivative of thiazolidine ring which came into existence for its role as antihyperglycemic agent and a specific ligand of PPAR's (Peroxisome proliferator activated receptor). Exhaustive research has led to determination of its vast biological profile with wide range of therapeutic applications. This review covers recent pharmacological advancements of thiazolidinedione moiety along with structure activity relationship so as to provide better correlation among different structures and their receptor interactions. [ABSTRACT FROM AUTHOR]