Garima Verma

The therapeutic voyage of pyrazole and its analogs: A review

Pyrazole, a five membered heteroaromatic ring with two nitrogen atoms is of immense significance. Presence of this nucleus in the pharmacological agents of diverse therapeutic categories viz. antianxiety, anti-inflammatory, antipsychotic, anticancer, antiobesity, analgesic, antipyretic etc. has made it an indispensable anchor for design and development of new pharmacological agents. Owing to the development of novel and new pyrazole based therapeutic agents at a faster pace, there is a need to couple the latest information with previously available information to understand status of this moiety in medicinal chemistry research. The review herein highlights the therapeutic worth of pyrazole derivatives. Several therapeutically active pyrazole based derivatives developed by numerous scientists across the globe are reported here.

A review exploring biological activities of hydrazones

The development of novel compounds, hydrazones has shown that they possess a wide variety of biological activities viz. antimicrobial, anticonvulsant, antidepressant, anti-inflammatory, analgesic, antiplatelet, antimalarial, anticancer, antifungal, antitubercular, antiviral, cardio protective etc., Hydrazones/azomethines/imines possess-NHN = CH- and constitute an important class of compounds for new drug development. A number of researchers have synthesized and evaluated the biological activities of hydrazones. This review aims at highlighting the diverse biological activities of hydrazones.

Piperazine scaffold: A remarkable tool in generation of diverse pharmacological agents

Piperazine is one of the most sought heterocyclics for the development of new drug candidates. This ring can be traced in a number of well established, commercially available drugs. Wide array of pharmacological activities exhibited by piperazine derivatives have made them indispensable anchors for the development of novel therapeutic agents. The review herein highlights the therapeutic significance of piperazine derivatives. Various therapeutically active piperazine derivatives developed by several chemists are reported here.

Therapeutic evolution of benzimidazole derivatives in the last quinquennial period

Benzimidazole, a fused heterocycle bearing benzene and imidazole has gained considerable attention in the field of contemporary medicinal chemistry. The moiety is of substantial importance because of its wide array of pharmacological activities. This nitrogen containing heterocycle is a part of a number of therapeutically used agents. Moreover, a number of patents concerning this moiety in the last few years further highlight its worth. The present review covers the recent work published by scientists across the globe during last five years.

The therapeutic journey of pyridazinone.

Pyridazinones have drawn a substantial attention within the field of research analysis and development. The moiety is a subject matter of intensive research because of its wide spectrum of biological activities and therapeutic applications. The synthesis of pyridazinone and investigation of their chemical and biological activities have gained additional importance in recent years. In this review, we have compiled and discussed various biological and therapeutic potential of pyridazinone derivatives.

Novel pyrazole-pyrazoline hybrids endowed with thioamide as antimalarial agents: their synthesis and 3D-QSAR studies.

Abstract One of the most viable options to tackle the growing resistance to the antimalarial drugs is hybrid molecules. It involves combination of different scaffolds in one frame that may lead to compounds with diverse biological profiles. In this context, new hybrids of three different scaffolds viz pyrazole, pyrazoline and thiosemicarbazone moiety were incorporated into one single compound and evaluated for their in vitro schizontocidal activity against the CQ-sensitive 3D7 strain of Plasmodium falciparum. Compounds with significant in vitro antimalarial activity were further evaluated for cytotoxicity against VERO cell lines. The best active compound 48 exhibited an IC50 of 1.13 µM. The in vitro results were further validated by quantitative structure–activity relationship (QSAR).

Malaria: Hitches and Hopes

Malaria, a devastating infectious disease caused by parasites of Plasmodium genera is transmitted from person to person through bites of infected mosquitoes. It generally traps underdeveloped nations with poor infrastructure and high population density. It has attracted considerable attention from academic institutions, pharmaceutical industries and government agencies but the efforts to eradicate this threat face a number of technical, economic, financial and institutional hurdles. In the absence of clinically proven vaccines to combat malaria, chemotherapy continues to be the best available option, although it suffers from a big loophole of resistance. Emergence of resistance is associated with the two phases of Plasmodiums life cycle: asexual in humans and sexual in mosquito, which are intricate to target simultaneously. Consequently, the search for novel antimalarial agents is a never-ending task for scientists and chemists. This review aims at highlighting the currently used antimalarial agents, targets for the therapy and present scenario in the development of new antimalarial drugs to combat this global problem.

Molecular interactions of dioxins and DLCs with the xenosensors (PXR and CAR): An in silico risk assessment approach

Dioxins and dioxin‐like compounds (DLCs) are known to cause endocrine disruption in humans and animals. Being lipophilic xenobiotic chemicals, they can be easily absorbed into the biological system from the surrounding environments, thereby causing various health dysfunctions. In the present study, a total of 100 dioxins and DLCs were taken, and their binding pattern was assessed with the xenosensors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in comparison with the corresponding known inhibitors and a well‐studied endocrine disrupting xenobiotic, bisphenol A (BPA). The nuclear receptors CAR and PXR are known to play a significant role in handling potential toxins by coordinating cellular transport and metabolic functions of the same. Among different endocrine‐disrupting chemicals used in the present study, DLCs (PCDFs and PCBs) elicited better interactions in comparison with the parent dioxin (polychlorinated dibenzodioxins) compounds. On comparing D scores of all the compounds against both the receptors, PCDF 8‐hydroxy‐3,4‐dichlorodibenzofuran (8‐OH‐DCDF) and PCB tetrachlorobenzyltoluene (TCBT) exhibited significant molecular interactions against PXR (−7.633 kcal mol−1) and CAR (−8.389 kcal mol−1), respectively. Predominant interactions were found to be H‐bonding, π‐π stacking, hydrophobic, polar, and van der Waals. By contrast, BPA and some natural ligands tested in this study showed lower binding affinities with these receptors than certain DLCs reported herein, ie, certain DLCs might be more toxic than the proven toxic agent, BPA. Such studies play a pivotal role in the risk assessment of exposure to dioxins and DLCs on human health.

Molecular Interactions of Bisphenols and Analogs with Glucocorticoid Biosynthetic Pathway Enzymes: An in silico Approach

Abstract Glucocorticoids are known to have vital effects on metabolism, behavior and immunity. Any sort of impairment in their synthesis may lead to the generation of numerous ill health effects. Different environmental toxicants, including bisphenols and their analogs pose deleterious effect on the biosynthesis of glucocorticoids, thereby leading to endocrine disruption. In order to assess the effect of these environmental toxicants on gluocorticoid biosynthetic pathway, an in silico study was performed. This involved molecular docking studies of 18 ligands with the selected participating enzymes of the pathway. These enzymes were CYP11A1, CYP11B2, CYP19A1, CYP17A1, 3α/20β-HSD, 3β/17β-HSD and CYP21A2. Comparison of their binding affinity was made with the known inhibitors of these enzymes. In case of CYP11A1, Bisphenol M (BP M) had the lowest docking score (D score) of −8.699 kCal/mol, and was better than that of the standard, Metyrapone. Bisphenol PH (BP PH) was found to have significant affinity with CYP11B2. In case CYP19A1, results were found to be comparable with the standards, Exemestane and Letrozole. BP PH elicited better results than the standard Abiraterone acetate against CYP17A1. BP M had a D score of −7.759 against 3α/20β-HSD, again better results than the standard, Trilostane. Upon molecular docking of BP PH against CYP21A2, it was seen that amongst all the analogs, it had maximum interactions along with the lowest D score. From all the above instances mentioned, it is quite evident that certain BPA analogs have more potential to modulate the enzymes involved in comparison to the known inhibitors.

Synthesis of Hybrids of Dihydropyrimidine and Pyridazinone as potential Anti-Breast Cancer Agents

BACKGROUND Different 3-aroylpropionic acids and dihydropyrimidine hydrazine derivatives were condensed together to yield a series of dihydropyrimidine and pyridazinone hybrids (5a-u). OBJECTIVE This was done in order to develop therapeutic agents for the treatment of breast cancer with improved Cycloxygenase-2 (COX-2) selectivity. In-vitro anticancer evaluation for these compounds was done against human breast cancer cell lines (MCF-7, MDA-MB-231) and normal human keratinocytes (HaCaT). CONCLUSION Amongst all the developed analogs, compound 5l emerged as the most potent agent against both these cell lines with IC50 values of 3.43 and 2.56 µM respectively. The synthesized compounds were also evaluated for COX-2 selectivity. To observe the binding pattern of the compounds with COX-2, a docking study was performed using PDB ID: 1CX2.