Pseudo-Natural product hypothesis is an emerging compound-design hypothesis for guiding the design of novel bioactive molecules. In this paper, we demonstrate the utilization of this hypothesis for the discovery of Indotropane as a novel class of antibacterial agent with activity against methicillin- and vancomycin-resistant S. aureus. This is one of the first examples of the demonstration of this hypothesis for the discovery of novel antibacterial agents. The lead compound (7af) was found to possess multiple favorable characteristics including in vivo activity.      

The first example of an Aza-Nazarov Cyclization/1,2-Wagner Meerwein Shift domino sequence for the synthesis of highly substituted pyrroles has been developed. The reaction shows substituent-dependent divergence in product formation to give indenes, besides pyrroles. The reaction is catalyzed by mild main group Bi(III) as the catalyst. It shows wide substrate scope. Mechanistic investigations reveal the role of 'Hidden Bronsted Acid" in co-catalyzing the reaction.    

Deciphering functional relevance of every protein is crucial to developing a better (patho)physiological understanding of human biology. Discovery and use of quality chemical probes propel exciting developments for developing drugs in therapeutic areas with unmet clinical needs. Myosin Light Chain Kinase (MLCK) serves as a possible therapeutic target in a plethora of diseases, including inflammatory diseases, cancer etc. Recent years have seen substantial increase in interest in exploring MLCK biology. However, there is only one widely used MLCK modulator, namely ML-7, that too with a narrow working concentration window and high toxicity profile leading to limited insights. Herein, we report the identification of a potent and highly selective chemical probe, Myokinasib-II, from the synthesis and structure-activity relationship studies of a focussed indotropane-based compound collection. Notably, it is structurally distinct from ML-7 and hence, meets the need for an alternative inhibitor to study MLCK biology as per the recommended best practices. Moreover, our extensive benchmarking studies demonstrate that Myokinasib-II displays better potency, better selectivity profile and no non-specific interference in relevant assays as compared to other known MLCK inhibitors. 

Highly arylated propeller-shaped heteroarenes constitute an intriguing class of molecular scaffolds for material science applications. Among these, tetraarylated furans demonstrate differentiated properties as compared to other similar heterocyclic cores. There are only a very limited number of methodologies available to access furans with four different (hetero)aryl substituents. Herein, we report the first methodology based on a sequential two-fold oxidative C-C coupling of furans with indoles to access bis(indolyl)furans (BIFs) - a new class of ‘extremely congested’ furans with up to four different substituents. The reaction is mediated by inexpensive, earth-abundant FeCl3.6H2O and displays high efficiency, wide substrate scope, modularity and aqueous compatibility. Moreover, we also present the first validation of the distinct aggregation-caused quenching (ACQ) property of the tetraarylated furans beyond only phenyls as peripheral groups and disclose new mechanistic underpinnings for the same. 

Sustainability is increasingly being factored into the design of chemical processes. Herein, we report the oxidative coupling between indoles and furans using extremely inexpensive catalyst CuCl2.2H2O (<0.25$ per g) in the presence of air for an expeditious synthesis of indolyl–furans. The reaction was found to work even under partially aqueous conditions. In addition, the methodology provides direct access to novel indole–furan–thiophene (IFT)-based electron-rich pi-conjugated systems, which show green-yellow fluorescence with large Stokes shift and high quantum yields. 

We report a general cross-dehydrogenative coupling between furans and indoles using earth-abundant metal catalyst FeCl3.6H2O in presence of oxygen. The reaction displayed scalability and aqueous compatibility, thus making it practical, operationally simple, and sustainable. The products were found to possess fluorescence properties with remarkable Stokes’ shift of upto 205 nm.  

SARS-CoV-2, the virus responsible for COVID-19, hijacks the metabolic machinery of the host cells, relying on their lipids and lipoproteins for entry, trafficking, immune evasion, viral replication, and exocytosis. The infection causes host cell lipid metabolic remodelling. Targeting lipid-based processes is, thus, a promising strategy for countering COVID-19. Here, we review the role of lipids in the different steps of the SARS-CoV-2 pathogenesis and identify lipid-centric targetable avenues. We summarize the emerging direct and indirect therapeutic approaches for targeting COVID-19 using lipid-inspired approaches. 

The paper describes the first-of-its-kind computational benchmarking of all known KIFC1 inhibitors against all the three proposed binding sites using the most resolved KIFC1 structural information. In addition, the most comprehensive review of the putative KIFC1 inhibitors reported to date in the literature is also presented along with a detailed analysis of the evolving biological profiles of each inhibitor chemotype. In this work, we show that α4/α6 is the most preferred binding site for the known KIFC1 inhibitors. Identification of the challenges in the development of novel KIFC1 inhibitors has been added to complete the review.

The identification of the pseudo-natural product Rhonin as the first small-molecule modulator of RHO GDP dissociation inhibitor (RHOGDI) is reported. Rhonin binds to RHOGDI and interferes with its function by disrupting the interaction between RHOGDI and RHO GTPases. 

Furan and Indole represent two of the most versatile heterocycles in organic chemistry. Herein, we report the first cross-dehydrogenative coupling of these two heterocycles catalyzed by copper in combination with aerial oxygen. Additionally, we also demonstrate a lesser known activating group effect of oxime ether substituent in oxidative coupling. 

Infectious diseases remain significant health concerns worldwide, and resistance is particularly common in patients with tuberculosis caused by Mycobacterium tuberculosis. Here, we comprehensively review recent advances in the development of membrane-active chemotypes that target mycobacterial membranes and discuss clinically relevant membrane-active antibacterial agents that have shown promise in counteracting bacterial infections. We discuss the relationship between the membrane properties and the synthetic requirements within the chemical scaffold, as well as the limitations of current membrane-active chemotypes. 

Furan occupies a position of eminence among heterocycles. Despite the availability of many methodologies for the synthesis of variably substituted furans, a modular convenient synthesis of 2,4-disubstituted furans remains challenging. The present work attempts to bridge that gap through a novel annulation-based approach using methyl ketones and β-bromoenol phosphates. We have demonstrated a hitherto unknown reactivity of β-bromoenol phosphates which is responsible for the observed regioselectivity. The methodology was applied to obtain synthetically challenging 3-acylfuran derivatives as well. 

Small-molecule chemotypes with unexpected bioactivity may be identified by combining strategies built on the biological relevance of natural products (NPs). Evaluation in target-agnostic phenotypic assays and target identification may link biologically relevant chemotypes to unexpected and unknown targets. We describe the phenotypic identification of an unprecedented kinase inhibitor chemotype, termed Myokinasib which impairs cytokinesis, induces formation of multinucleated cells, and reduces phosphorylated myosin II light chain abundance on stress fibers by selective inhibition of myosin light chain kinase 1.