Debasis Manna

• PhD
• Professor at Indian Institute of Technology Guwahati

With N-tosylhydrazone as an ambiphilic reagent, an unprecedented cyclization reaction of two identical or different tosylhydrazones has been developed to access various 4,5-disubstituted-2H-triazoles under transition metal, azide, and oxidant-free conditions. A mechanistic rationalization study led to the identification of several electronically di...

We describe a novel class of amphiphiles with squaramide moiety as a phosphate bioisostere. Most synthesized squaramide-based amphiphiles have the favorable physicochemical properties of lipids, such as: formation of stable liposomes or giant unilamellar vesicles in aqueous solution, high phase-transition temperature, low vesicle leakage and phosph...

Uncontrolled metabolism of L-tryptophan (L-Trp) in the immune system has been recognized as a critical cellular process in immune toler-ance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local L-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic t...

Tryptophan metabolism through the kynurenine pathway is considered as a crucial mechanism in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism in the immune system and it is also considered as an important therapeutic target for the treatment of cancer and other diseases that are linked with kynurenine...

Artificial ion channels have significant potential for various applications, including molecular communication, bio‐sensing, and constructing artificial cells. In this report, we demonstrated the development of a molecular communication system that transports ions across the lipid bilayers via the formation of supramolecular ion channels and harnes...

Artificial ion channels have significant potential for various applications, including molecular communication, bio‐sensing, and constructing artificial cells. In this report, we demonstrated the development of a molecular communication system that transports ions across the lipid bilayers via the formation of supramolecular ion channels and harnes...

The development of synthetic ion channels and stimuli‐responsive suprasomes represents two crucial yet largely disconnected areas of supramolecular chemistry. Herein, we demonstrated that suprasomes can effectively deliver hydrophobic synthetic ion transporters to lipid membranes, regulating physiologically significant transition metal ions and sub...

The recovery of dwindling materials from wastewater could be helpful in resolving the rising need for resources in society. Phosphate is a nutrient that all living organisms require, but a...

Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has emerged as a promising therapeutic strategy for both cancer and Alzheimer's disease due to its critical role in modulating immune response and neurodegenerative processes....

The escalating prevalence of bacterial infections presents a formidable challenge to current global healthcare systems. Rapid identification and quantification of bacterial pathogens with anticipated sensitivity and selectivity are crucial for targeted therapeutic interventions to mitigate disease burden, drug resistance, and further transmission....

Cis‐5,15‐bis(3,5‐trifluoromethylphenyl)calix[4]pyrrole (1) forms stable 1/1 complexes with linear anions such as N3⁻, SCN⁻ and NCO‐ with the highest affinity for NCO⁻ anion in acetonitrile solution. Crystallization of receptor 1 with TBASCN and (TMA)2SO4 resulted in the formation of dimeric capsular assembly, {(TMA)2[12 ⋅ (SCN)2]}, in which two thi...

The light and pH dual-responsive ion transporters offer better applicability for cancer due to higher tunability and low cytotoxicity. Herein, we demonstrated the development of pH-responsive β-carboline-based ionophores and photocleavable-linker...

Phosphate is one of the essential nutrients for the growth of various organisms. However, it increasingly infiltrates aquatic environments due to human activities, posing environmental risks. Recovering phosphates from wastewater...

A molecular switch was developed to recognize and transport Cl‒ across lipid bilayers. The XRD-crystal structure and NOESY NMR spectra of the potent 4-aminoquinazoline analogue confirmed Cl‒-induced conformation changes. Systematic...

Augmentation of the activity of Food and Drug Administration‐approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic‐resistant bacteria. This study reports the development of sulfonium‐cross‐linked hyaluronic acid (HA)‐based polymer (HA‐SS‐HA) as an inherent antimicrobial a...

Integrin-mediated cellular delivery was attempted to optimize practical applications of hydrophobic ionophores. The potent ionophore preferentially transports H+/Cl− across the lipid bilayers following a symport mechanism. The RGD-peptide-appended tag was...

Visceral Leishmaniasis (VL) is a severe form of leishmaniasis, primarily affecting the poor in developing countries. Although several studies highlighted the importance of toll-like receptors (TLRs) in the pathophysiology of leishmaniasis, however, the role of specific TLRs and their binding partners involved in Leishmania donovani uptake are still...

Host-guest complexation-based suprasomes successfully deliver benzimidazolium amphiphile. The β-CD and Zn2+ or acidic environment acts as the stimuli for the assembly and disassembly of suprasomes. The supramolecular nanomedicine developed by...

Herein, we report the development of synthetically simpler analogs of 4,7-dichloroquinoline (DCQ) as apo-indoleamine 2,3-dioxygenase 1(IDO1) protein targeting ligand to inhibit the activity of IDO1 enzyme. Derivatization of the DCQ moiety improved the IDO1 inhibitory activity both against purified enzyme and the cellular environment without any sig...

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and...

Meso-3,5-bis(trifluoromethyl)phenyl picket calix[4]pyrrole 1 displayed excellent fluoride anion transport activity across the artificial lipid bilayers showing EC50 = 2.15 μM (at 450 sec in EYPC vesicle) with high fluoride over...

Palladium is a key element in fuel cells, electronic industries, and organic catalysis. At the same time, chromium is essential in leather, electroplating, and metallurgical industries. However, their unpremeditated leakage into aquatic systems has caused human health and environmental apprehensions. Herein, we reported the development of an sp² ca...

Increasing evidence supports vanillin and its analogs as potent toll-like receptor signaling inhibitors that strongly attenuate inflammation, though, the underlying molecular mechanism remains elusive. Here, we report that vanillin inhibits lipopolysaccharide (LPS)-induced toll-like receptor 4 activation in macrophages by targeting the myeloid diff...

Multifunctional drug delivery systems are the centerpiece of effective chemotherapeutic strategies. Herein, we report the synthesis of an acetazolamide-linked cyanine-3-based NIR-responsive fluorescent macrocyclic amphiphile that self-assembled into spherical nanostructures in the aqueous medium via a J-aggregation pattern. The amphiphile shows var...

The higher hydration energy of phosphate anions restricts their transmembrane transport activities. Herein, we report the development of 2-benzimidazolylthiourea-based scaffolds displaying good efficacy in phosphate transport than Cl- ion transport and following phosphate/Cl- antiport pathways. This alteration of anion homeostasis showed induction...

We describe the development of bis-guanidinium-based synthetic chloride-phosphate ion carriers. Photoinduced generation of the active anionophore from proanionophore enhanced the transport of chloride-phosphate ions across the lipid bilayers and promoted cancer (HeLa) cell death. Such photoactivatable chloride-phosphate antiporters could be helpful...

Retrieval of depleting resources from wastewater could resolve its mounting demands in our society. Phosphate is an essential nutrient for all living things. However, the diminution of global reserves of...

Anticancer drug resistance implicates multifunctional mechanisms, and hypoxia is one of the key factors in therapeutic resistance. Hypoxia-specific therapy is considered an extremely effective strategy to fight against cancer. The development of small molecule-based synthetic anion transporters has also recently drawn attention for their potential...

The devastating antibacterial infections, coupled with their antibiotic resistance abilities, emphasize the need for effective antibacterial therapeutics.

We developed NIR-light-responsive macrocyclic cationic gemini amphiphiles, one of which displayed various favorable properties of lipids. The NIR-light-mediated cleavage of the strained dioxacycloundecine ring led to the conversion of the spherical to a nanotubular self-assembly in the aqueous medium. This photo-mediated transformation from the sph...

Inhibition of immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is considered one of the potential approaches in the fight against cancer and other diseases. Comprehensive biophysical and cellular studies have shown that quinine derivatives effectively inhibit the activity of IDO1. Mechanistic studies revealed that the potent quinine der...

In recent times, anion transporters have received substantial consideration due to their ability to disrupt the ionic equilibrium across membrane bilayers. While numerous Cl⁻ ion transporters were developed for channelopathies, unfortunately, poor aqueous solubility precluded their bioapplicability. Herein, we demonstrate the development of a multi...

The use of synthetic ion transporters for alteration of the concentration of ions across cell membranes has drawn attention from scientists over the last two decades. This ion transport property has been sensibly used to reduce the viability of cancer cells mainly due to the disruption of their ion homeostasis, leading to the perturbation of their...

Tumor cells promote immune evasion through up regulation of PD-L1 that binds with PD1 on cytotoxic T cells and promote dysfunction. Though therapeutic efficacy of anti PD1 antibody has remarkable effects on different type of cancers it is less effective in breast cancer. Hence more details understanding of PD-L1 mediated immune evasion is necessary...

Synthetic ion transporters have attracted tremendous attention for its therapeutic potentials against various ion transport-related diseases, including cancer. Inspired by the structure and biological activities of natural products, we synthesized a small series of squaramide and thiourea derivatives of quinine and investigated their ion transport...

Small molecule-based Cl─ ion carriers are relishing a revived attention because of their recently discovered role towards the anticancer activity. Herein, we showed that the anticancer agents, PITENINs, have an efficient transmembrane Cl─ ion transport activity. Theoretical calculations, 1H NMR titration, and spectrophotometric analysis suggest tha...

We describe a novel class of stimuli-sensitive synthetic lipids, which possesses several favorable biophysical properties of phospholipids. The sulfonium-based lipid was successfully disassembled by glutathione to release the encapsulated drug molecules in a controlled manner. The cationic lipid also showed lower cytotoxicity against mammalian cell...

We describe a novel class of stimuli-sensitive sulfonium-based synthetic lipids, which exhibit several favorable biophysical properties of phospholipids. The potent sulfonium-based lipid was successfully disassembled by glutathione to release the encapsulated drug molecules in a controlled manner. The cationic lipid also showed lower cytotoxicity a...

The design of green synthetic reaction conditions is very challenging, especially for biomaterials, but worthwhile if the compounds can be easily synthesized in the aqueous medium. Herein, we report the development of sunlight-mediated thiol–ene/yne click reaction in the presence of a catalytic amount of tert-butyl hydroperoxide (TBHP) in an aqueou...

The improvement of body’s own immune system is considered one of the safest approaches to fight against cancer and several other diseases. Excessive catabolism of the essential amino acid, L-tryptophan (L-Trp) assists the cancer cells to escape normal immune obliteration. The formation of disproportionate kynurenine and other downstream metabolites...

Stimuli-responsive anion transport strategy was successfully employed to regulate water solubility and promote controlled transport of Cl─ ion across the lipid bilayers. The sulfonium-based proanionophore was efficiently activated by glutathione...

Recently synthetic anion transporters have gained considerable attention because of their aptitude to disrupt cellular anion homeostasis and promote cell death. Herein, we report the development of bis(iminourea) derivatives as a new class of selective Cl– ion carrier. The cooperative interactions of H+ and Cl– ions with these iminourea moieties re...

Protein based nanostructures has reformed the nanoscience and nanotechnology on the account of their smaller sizes and greater surface areas, which instigates their interactions with other molecules. The protein nanoparticles (NPs) have better biocompatibility, biodegradability and also have the easy access for additional surface modifications. The...

Synthetic anion transporters have been recognized as one of the potential therapeutic agents for the treatment of diseases including cystic fibrosis, myotonia and epilepsy that originate due to the malfunctioning of natural Cl─ ion transport systems. Recent studies showed that the synthetic Cl─ ion transporters can also disrupt cellular ion-homeost...

An unusual transformation of indoles to pyrazoles via an aromatic ring-opening strategy has been developed. The salient feature of this strategy involves the C2-N1 bond opening and concomitant cyclization reaction of the C2=C3 bond of the indole moiety with the tosylhydrazone which proceeds under transition-metal and ligand free conditions. This ri...

Indoleamine 2,3‐dioxygenase 1 (IDO1) plays pivotal role in regulating the metabolism of L‐tryptophan (L‐Trp) through kynurenine pathway, which is a well‐established therapeutic target for the treatment of diseases associated with immunosuppression. Disproportionate expression of the enzyme and poor prediction of various types of malignancies make t...

In the present study, medicinal phytochemicals found in plants of north-eastern India were virtually screened against the C1b regulatory domain of Protein Kinase C (PKC), an important enzyme in cancer cell-biology. Amongst the few top hits, the molecules Gallic acid (GA) and Epigallocatechin gallate (EGCG) were identified through an agonist competi...

Tyrosine kinase substrate with 5 Src homology 3 domains (Tks5) regulates several important cellular functions and is crucial for invadosome formation. The phox homology (PX) domain of Tks5 interacts with phosphatidylinositols (PIPs) and essential for Tks5-induced invadosome formation. However, PIP-binding specificity of the Tks5-PX domain is not cl...

Chemical libraries constitute a reservoir of pharmacophoric molecules to identify potent anti-cancer agents. Virtual screening of heterocyclic compound library in conjugation with the agonist-competition assay, toxicity-carcinogenicity analysis, and string-based structural searches enabled us to identify several drugs as potential anti-cancer agent...

Overexpression of the immunosuppressive enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) is associated with poor prognosis of patients for a wide range of malignancies. IDO1 is a validated target for the treatment of diseases that are associated with immune suppression, including cancer. In this report, we described the synthesis of a series of C3- sub...

Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of IDO1 enzyme revealed that conversion of L-tryptophan (L-Trp) to N-formylkynurenine proce...

Chlorogenic acid (CGA) exhibits potentials towards liver, breast and skin cancer. Cancer cells stimulated with CGA exhibits differential expression of transcriptional factors and regulatory molecules but the molecular target of the molecule is not known. Superposition of biophoric elements of CGA with Curcumin gives maximum common substructure scor...

Danazol, the established clinical drug has given promising therapeutic results in a series of clinical trials with breast cancer patients. Danazol shares structural similarities with several known PKC agonists and fits well into the C1 domain. Danazol binds to the C1b domain of PKC with Kd of 5.64±1.27 μM. MD simulation studies further support that...

Purpose The protein kinase C (PKC) family of serine-threonine kinases plays an important role in cancer cell progression. Thus, molecules that target PKC have potential as anticancer agents. The current study aims to understand the treatment of breast cancer cells with alkyl cinnamates. We have also explored the mechanistic details of their antican...

Aim: The therapeutic treatment of microbial infections involving biofilm becomes quite challenging because of its increasing antibiotic resistance capacities. Towards this direction, in the present study we have evaluated the anti biofilm property of synthesized 3-amino-4-aminoximidofurazan compounds having polyamine skeleton. These derivatives we...

Lamellipodin (Lpd) protein plays an important role in the formation of lamellipodial protrusion which is crucial in actin dynamics, cell polarity and motility. Lpd promotes actin polymerization with the help of members of the Ena/VASP family of actin regulators and tethering them to actin filaments. It is well documented that Lpd protein interacts...

Aberrant regulation of phosphatidylinositol-3-kinases (PI3K) dependent cell signalling pathways is directly linked with different human cancers. AKT is a phosphatidylinositol (PI) binding serine/threonine kinase enzyme and a key component of PI3K-signalling pathway. Several efforts have been made to perturb the activities of AKT enzyme; however, se...

Background Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is an important regulator of several cellular processes and a precursor for other second messengers which are involved in cell signaling pathways. Signaling proteins preferably interact with PI(4,5)P2 through its pleckstrin homology (PH) domain. Efforts are underway to design small molecu...

The protein kinase C (PKC) family of proteins is considered as an attractive drug target. Dysregulation of PKC-dependent signalling pathways are related with several human diseases like cancer, immunological and other diseases. We have been approaching this problem of altering PKC activities by developing C1 domain-based PKC ligands. In this report...

The synthesis of 1H-indazoles from o-aminobenzoximes is achieved via N-N bond formation using triphenylphosphine, 12, and imidazole. Selective formation of oxime-phosphonium ion intermediate in the presence of the amino group is the driving force for this reaction. The nucleophilicity of the arylamino group and electrophilicity toward the N-O bond...

Protein kinase C (PKC) family of lipid-activated kinases plays a significant role in the regulation of diverse cellular functions including tumor promotion, apoptosis, differentiation, and others. The lipophilic second messenger diacylglycerols (DAGs) acts as endogenous ligand for the PKCs in the presence of anionic phospholipids. To develop effect...

Protein kinase C (PKC)-C1 domain targeted regulator development is considered as a potential therapeutic strategy for the treatment of cancer, immunological and other diseases. Efforts are underway to synthesize small molecules to achieve higher specificity for the C1-domain than the natural activator, diacylglycerols (DAGs). In this regard, we con...

Development of protein kinase C (PKC) regulators has been considered as an attractive therapeutic strategy for the treatment of cancer and other diseases. Extensive efforts are underway to synthesize PKC regulators targeted to the DAG-responsive C1 domain. Investigation of physicochemical properties of the synthesized molecules also is essential fo...

We describe the synthesis of diacyltetrol-based hybrid lipids in which one of the hydroxymethyl groups is modified with an anionic phospholipid headgroup. The hybrid lipids form a monolayer at the air–water interface. In aqueous solution, these lipids form stable liposomes that exhibit a negative surface potential across a wide pH range. The liposo...

This is mild and highly chemoselective method for the esterification and amidation of aromatic and aliphatic carboxylic acids.

Selective esterification of aliphatic and aromatic carboxylic acids with various alcohols is studied using triphenylphosphine, I2, and a catalytic amount of Zn(OTf)2. Use of this catalyst allows the formation of esters at a faster rate with good to excellent yield by activating the in situ generated acyloxyphosphonium ion intermediate. During the e...

Diacylglycerol (DAG) regulates a broad range of cellular functions including tumor promotion, apoptosis, differentiation, and growth. Thus, the DAG-responsive C1 domain of protein kinase C (PKC) isoenzymes is considered to be an attractive drug target for the treatment of cancer and other diseases. To develop effective PKC regulators, we convenient...

Cu(II) complexes of three tridentate ligands, L(1), L(2) and L(3), [L(1), N-((1H-imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(2), N-((1-methyl-1H-imidazole-2-yl)methyl)-2-(pyridine-2-yl)ethanamine; L(3), 2-(pyridine-2-yl)-N-((pyridine-2-yl)methyl)ethanamine] respectively, were synthesized and characterized. The single crystal X-ray structu...

Nucleotides whose mutations seriously affect glutamylation efficiency are experimentally known for Escherichia coli tRNA(Glu). However, not much is known about functional hotspots on the complementary enzyme, glutamyl-tRNA synthetase (GluRS). From structural and functional studies on an Arg266Leu mutant of E. coli GluRS, we demonstrate that Arg266...

The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Diacylglycerol (DAG), phorbol esters and others act as ligands for the C1 domain of PKC isoforms. Inspection of the crystal structure of the PKCδ C1b subdomain in complex with phorbol-13-O-acetate shows that one...

The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Natural product curcumin is known to interact with PKC isoforms through the C1 domain and modulate PKC activity. The reported results demonstrate that the symmetric curcumin molecule might act as two separate un...

Membrane lipids act as important regulators of a litany of important physiological and pathophysiological events. Many of them act as site-specific ligands for cytosolic proteins in binding events that recruit receptors to the cell surface and control both protein function and subcellular localization. Phosphatidylinositol phosphates (PIP(n)s) are...

Many cytosolic proteins are recruited to the plasma membrane (PM) during cell signaling and other cellular processes. Recent reports have indicated that phosphatidylserine (PS), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) that are present in the PM play important roles fo...

The spectrin cytoskeleton assembles within discrete regions of the plasma membrane in a wide range of animal cell types. Although recent studies carried out in vertebrate systems indicate that spectrin assembly occurs indirectly through the adapter protein ankyrin, recent studies in Drosophila have established that spectrin can also assemble throug...

Phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) are lipid second messengers that regulate various cellular processes by recruiting a wide range of downstream effector proteins to membranes. Several pleckstrin homology (PH) domains have been reported to interact with PtdIns(3,4)P2...

Phospholipase A(2)s (PLA(2)s) are a superfamily of enzymes involved in production of a wide variety of lipid mediators, including arachidonic acid, lysophospholipids, platelet activation factor, and eicosanoids. Fluorescence-based, real-time cellular activity assays for PLA(2)s have been developed as a tool for studying the function and spatiotempo...