Aaftaab Sethi

Adam Mickiewicz University | UAM

A novel series of imidazo[2,1-b]thiazole-sulfonyl piperazine conjugates (9aa-ee) has been synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory potency against four isoforms: The cytosolic isozyme hCA I, II and trans-membrane tumor-associated isoform hCA IX and hCA XII, taking acetazolamide (AAZ) as standard drug, using a sto...

For the first time, inclusion has been crafted between a carbohydrate based molecule and β-CD hydrophobic cavity for the asymmetric catalytic applications. This novel D-glucosamine based inclusion compound has been synthesized in high yields using innovative and proficient acoustic cavitation technology and well characterized by using various techn...

The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has been rapidly transmitting and leaving its footprints across the globe. Stringent measures like complete lockdown and extensive testing have been employed by many countries to slow it down in its tracks until a viable treatment is found. Therefore, in the current scenario, prompt...

In continuation of our quest to develop non-carbohydrate galectin-1 inhibitors, we have designed and synthesized 20 indole-coumarin hybrids linked via chalcone. Compounds 6i and 7e were found to decrease galectin-1 levels significantly in galectin-1 enzyme assay at 20 µM concentration. Binding affinity studies carried out by fluorescence spectrosco...

Introduction – Galectins are ubiquitous in nature. They have established themselves as a protein family of high therapeutic potential. They have been found to play a role in a wide variety of diseases like cancer, fibrosis, and Alzheimer’s. Within the galectin family, galectin- 1 and galectin- 3 have been widely studied and their roles and function...

Sugar mimics are valuable tools in medicinal chemistry, offering the potential to overcome the limitations of carbohydrate inhibitors, such as poor pharmacokinetics and non-selectivity. In our continued efforts to develop heterocyclic galectin-1 inhibitors, we report the synthesis and characterization of thiazole-linked coumarin piperazine hybrids...

Protein hydration plays a vital role in many biological functions, and molecular dynamics simulations are frequently used to study it. However, the accuracy of these simulations is often sensitive to the water model used, a phenomenon particularly evident in intrinsically disordered proteins. Here, we investigated the extent to which the choice of...

Computational approaches have transformed many aspects of drug discovery in the past. With the advent of big data and artificial intelligence (AI), computational technology for drug discovery has again gained the forefront. DeepMind's “AlphaFold”, an AI-based system made headlines when it achieved unprecedented accuracy in determining the 3D struct...

Experimental approaches for identifying protein structures and conducting their analyses face systemic limitations and challenges. Thus, computational approaches have emerged as invaluable tools over the past few decades, offering complementary insights into the protein structure, function and analysis. This chapter provides a focused overview of c...

Matrix Metalloproteinases-9 (MMP-9) is one of the important targets that play a vital role in various diseases such as cancer, Alzheimer’s, arthritis, etc. Traditionally, MMP-9 inhibitors have been unable to achieve selectivity to get around this target; thereby, novel mechanisms such as inhibition of activated MMP-9 zymogen (pro-MMP-9) have been d...

Background: Carbonic Anhydrase (CA) are a family of metalloenzymes that catalyze the reversible interconversion of CO2 and water to bicarbonate and proton. CA isoforms I, II, IX, and XII are considered physiologically and pharmacologically relevant. Objective: The objective of this study is to synthesize potent and selective tumor-associated CA...

A series of pyranopyrazoles were synthesized via a one-pot four-component approach. The reaction was catalyzed by a β-CD/Yb(OTf)3 dual catalytic system. The protocol demonstrated offers several advantages, such as short reaction times, excellent yields, good functional group tolerance, ambient and environmentally benign conditions, scalability, and...

With the economic and societal progress, a great escalation in energy demands has been witnessed over the years. A major proportion of total energy consumed globally is accounted by the transportation sector where fossil fuels or derivatives such as petrol, diesel and jet fuel are predominantly utilized. This has led to a very high contribution to...

Herein, we report a metal-free protocol for the activation of nitrile towards the nucleophilic addition and subsequent annulation under an aqueous medium for the first time. The protocol divulges an efficient route for the construction of diversified aminated isoquinolines. Differently substituted primary as well as secondary amines underwent the r...

In the recent past, chitosan demonstrated intriguing applications in the different domains of biomedical science, probably due to its biodegradability, biocompatibility, minimal toxicity, cost-effectiveness, and easy-going synthetic procedures. Chitosan is the second most prevalent amino polysaccharide after cellulose, generated from a deacetylated...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has generated a critical need for treatments to reduce morbidity and mortality associated with this disease. However, traditional drug development takes many years, which is not practical solution given the current pandemic. Therefore, a viable option is to repurpose existing...

In the dire need of novel inhibitors of enzymes, computational approaches have significantly expedited the drug discovery process. Aspartic protease enzymes of Plasmodium falciparum such as plasmepsin II (PfPlm II) and plasmepsin IV (PfPlm IV) have been recognized as an attractive drug target for antimalarial drug discovery. In line with this, we p...

Herein, we report a metal/additive-free protocol for the activation of nitrile towards the nucleophilic addition and subsequent annulation under an aqueous medium for the first time. The protocol divulges an...

Novel coronavirus disease 2019 (COVID-19) has significantly altered the socio-economic status of countries. Although vaccines are now available against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent for COVID-19, it continues to transmit and newer variants of concern have been consistently emerging world-wide. C...

In drug discovery applications, high throughput virtual screening exercises are routinely performed to determine an initial set of candidate molecules referred to as “hits”. In such an experiment, each molecule from a large small-molecule drug library is evaluated in terms of physical properties such as the docking score against a target receptor....

In drug discovery applications, high throughput virtual screening exercises are routinely performed to determine an initial set of candidate molecules referred to as "hits". In such an experiment, each molecule from large small-molecule drug library is evaluated for physical property such as the docking score against a target receptor. In real-life...

Lectins are a family of glycan-binding proteins, many of which have been established as key targets for therapeutic intervention. They play a central role in many physiological and cellular processes. With the advances in protein crystallography, NMR spectroscopy and computational power over the past couple of decades, the carbohydrate-receptor int...

In drug discovery applications, high throughput virtual screening exercises are routinely performed to determine an initial set of candidate molecules referred to as "hits". In such an experiment, each molecule from large small-molecule drug library is evaluated for physical property such as the binding affinity (docking score) against a target rec...

In continuation of our quest to develop synthetically viable galectin-1 inhibitors, we constituted an extensively curated 3D-QSAR model involving galectin-1 inhibitors. Training and validation of QSAR predictive model was performed on a master dataset consisting of 52 compounds. The molecular structures and binding affinities of the compounds were...

Galectin-3 is a carbohydrate-binding protein that plays a crucial role in cancer and fibrosis. Its inhibitors have largely evolved from naturally occurring saccharides to many synthetic forms with significantly improved affinity. However, there haven't been any substantial and sizeable structure-activity relationship studies in order to develop pot...

The Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) spread like wildfire throughout the globe and continues to do so. Stringent measures like complete lockdown and extensive testing have been employed by many countries to slow it down in its tracks as no viable treatment is available till date. Therefore, in the current scenario, prom...

With an aim to develop potent lead molecules as a novel class of reverse transcriptase (RT) inhibitors, we have synthesized amide and ether conjugates of 2,3‐diaryl‐1,3‐thiazolidin‐4‐one derivatives. The compounds 9a and 9f exhibited IC50 values of 0.21113 ± 0.013μM and 12.6804 ± 0.062μM respectively from the in vitro human immunodeficiency virus t...

Global HIV statistics by World Health Organization (WHO) for the year 2017 was estimated to be 36.9 (31.1–43.9) million. Antiviral drug resistance poses a serious threat to the public health and requires immediate action. Retroviral integrase (IN) a component enzyme in the retroviral pre-integration complex (PIC) enables a retrovirus to incorporate...

The process of hunt of a lead molecule is a long and a tedious process and one is often demoralized by the endless possibilities one has to search through. Fortunately , computational tools have come to the rescue and have undoubtedly played a pivotal role in rationalizing the path to drug discovery. Of all techniques, molecular docking has played...

β-Cyclodextrin immobilized amino sugar was prepared by sonicating the mixture of β-CD and amino sugar for 15 min in Ethanol- Water (1/1,v/v). This reaction mixture was further lyophilized to obtain the solid inclusion complex. The formation of the Inclusion Complex (IC) was supported by using standard techniques such as FT-IR, UV-visible absorption...