Susanta Adhikari

Bio: Susanta Adhikari is an academic researcher from University of Calcutta. The author has contributed to research in topics: Cytotoxicity & Docking (molecular). The author has an hindex of 5, co-authored 10 publications receiving 102 citations.

A FRET based colorimetric and fluorescence probe for selective detection of Bi3+ ion and live cell imaging

Abstract: A Rhodamine B- quinoline conjugate (RSQ) functions as a colorimetric and fluorescence probe for selective recognition of Bi3+ ion based on CHEF assisted FRET process. RSQ visibly changes its colour and fluorescence profile upon addition of Bi3+ ion. The distinctive colour change allows facile discrimination of Bi3+ over other common cations. Lowest concentration of Bi3+ detected by RSQ is 0.05 μM. RSQ efficiently images intracellular Bi3+ in live SiHa cells.

Oestrogen receptor-mediated liposomal drug delivery for treating melanoma.

Abstract: Function of steroid hormone oestrogen that transactivates oestrogen receptor (ER) is expressed in multiple organs. Except for malignancies of gynaecological organs, ER remains largely unutilised as a target to treat cancers of ER-expressing brain, prostate, skin etc. We have previously developed oestrogen targeting cationic lipid molecule (ES-C10), which showed targeted killing of ER + breast and skin cancer cells. In this study, we explored the targeting ability of ES-C10 as a ligand as well as its additive killing effect (if any), when incorporated in two different liposomes (DCME and DCDE), carrying two anticancer molecules MCIS3 and Docetaxel™, respectively. DCME and DCDE exhibited higher cytotoxicity in ER + cancer cells than in ER − cancer or in non-cancer cells. Both liposomes induced ER-mediated cytotoxicity and caspase 3-induced apoptosis in ER + melanoma cells. Further, decreased levels of pAkt, and increased levels of PTEN and p53 were also observed. Both the targeted liposomes were lea...

X-ray structurally characterized quinoline based fluorescent probes for pH sensing: Application in intracellular pH imaging; DFT calculations and fluorescent labelling

Abstract: Quinoline based fluorescent probes QNOH-MO and QNOH-OME were synthesized, and their photo-physical properties were carefully investigated. The probes were well characterized by 1H-NMR, 13C-NMR, ESI-MS, and single-crystal X-ray structure analysis. QNOH-MO and QNOH-OME can identify small changes in pH by colorimetric and fluorescence methods. In low pH range, these probes display a red fluorescence in both live and fixed cells. However, with increasing pH, the observed red fluorescence decreased with a simultaneous increase in green fluorescence. The pH-dependent switching from red to green fluorescence is well supported by theoretical calculations and 1H NMR titration experiments. Furthermore, the ability of these probes to image pH changes in live cells was also scrutinized. Moreover, QNOH-OME was successfully utilized for fluorescent labelling of cholesterol molecule which is an important component of biological membranes and is used in the liposomal formulation for drug delivery applications. Additionally, QNOH-MO was quaternized to induce an intrinsic cationic property to the molecule. The cationic probe QNOH-MO-CA exhibited improved water solubility and pH sensing efficiency.

The future of aminoglycosides: the end or renaissance?

Abstract: Although aminoglycosides have been used as antibacterials for decades, their use has been hindered by their inherent toxicity and the resistance that has emerged to these compounds. It seems that such issues have relegated a formerly front-line class of antimicrobials to the proverbial back shelf. However, recent advances have demonstrated that novel aminoglycosides have a potential to overcome resistance as well as to be used to treat HIV-1 and even human genetic disorders, with abrogated toxicity. It is not the end for aminoglycosides, but rather, the challenges faced by researchers have led to ingenuity and a change in how we view this class of compounds, a renaissance.

Bacterial lipid membranes as promising targets to fight antimicrobial resistance, molecular foundations and illustration through the renewal of aminoglycoside antibiotics and emergence of amphiphilic aminoglycosides

Abstract: Hereunder, we highlight bacterial membrane anionic lipids as attractive targets in the design of antibacterial drugs which can be effective against both Gram-positive and Gram-negative resistant bacteria. In this approach, first, molecular foundations and structure–activity relationships are laid out for membrane-targeting drugs and drug candidates from the structure and physicochemical properties of the main membrane targets, describing, as well, the corresponding identified resistances. Second, this approach is illustrated by the history of the emergence of antibacterial and antifungal amphiphilic aminoglycosides (AAGs) which are active against Gram-positive and Gram-negative resistant bacteria. AAGs have resulted from intensive medicinal chemistry development of a group of old antibiotic drugs known as aminoglycosides (AGs), which target ribosomal RNA. The aforementioned AAG's are being used towards discovering new antibiotics which are less toxic and less susceptible to resistance. The recent results in the field of AAGs are described and discussed in terms of structure–activity relationships and mechanism of action.

Designer aminoglycosides: the race to develop improved antibiotics and compounds for the treatment of human genetic diseases

Abstract: Aminoglycosides are highly potent, broad-spectrum antibiotics that exert their bactericidal therapeutic effect by selectively binding to the decoding aminoacyl site (A-site) of the bacterial 16 S rRNA, thereby interfering with translational fidelity during protein synthesis. The appearance of bacterial strains resistant to these drugs, as well as their relative toxicity, have inspired extensive searches towards the goal of obtaining novel molecular designs with improved antibacterial activity and reduced toxicity. In the last few years, a new, aminoglycoside dependent therapeutic approach for the treatment of certain human genetic diseases has been identified. These treatments rely on the ability of certain aminoglycosides to induce mammalian ribosomes to readthrough premature stop codon mutations. This new and challenging task has introduced fresh research avenues in the field of aminoglycoside research. Recent observations and current challenges in the design of aminoglycosides with improved antibacterial activity and the treatment of human genetic diseases are discussed.

Strategies to overcome the action of aminoglycoside-modifying enzymes for treating resistant bacterial infections

Abstract: Shortly after the discovery of the first antibiotics, bacterial resistance began to emerge. Many mechanisms give rise to resistance; the most prevalent mechanism of resistance to the aminoglycoside (AG) family of antibiotics is the action of aminoglycoside-modifying enzymes (AMEs). Since the identification of these modifying enzymes, many efforts have been put forth to prevent their damaging alterations of AGs. These diverse strategies are discussed within this review, including: creating new AGs that are unaffected by AMEs; developing inhibitors of AMEs to be co-delivered with AGs; or regulating AME expression. Modern high-throughput methods as well as drug combinations and repurposing are highlighted as recent drug-discovery efforts towards fighting the increasing antibiotic resistance crisis.

A New Strategy: Distinguishable Multi-substance Detection, Multiple Pathway Tracing Based on a New Site Constructed by the Reaction Process and Its Tumor Targeting

Abstract: In recent years, it has become a trend to employ organic molecular fluorescent probes with multireaction sites for the distinguishable detection and biological imaging of similar substances. However, the introduction of multireaction sites brought great challenges to organic synthesis, and at the same time, often destroyed the conjugated structure of the molecules, leading to an unsatisfactory fluorescence emission wavelength not conducive to practical application. As the eternal theme of life, metabolism goes on all the time. Metabolism is a series of ordered chemical reactions that occurs in the organism to maintain life. Chemical reactions in metabolism can be summarized as metabolic pathways. Simultaneous monitoring of different metabolic pathways of the same substance poses a lofty challenge to the probe. Here, we developed a new strategy: to construct new sites through the preliminary reactions between probes and some targets, which can be used to further distinguish among targets or detect their metabolites, so as to realize the simultaneous visualization tracer of multiple metabolic pathways. By intravenous injection, it revealed that the probe containing benzopyrylium ion can target tumors efficiently, and thiols are highly expressed in tumors compared to other tissues (heart, lung, kidney, liver, etc.). The consumption of thiols by the probe could not prevent tumor growth, suggesting that the tumor cure was not correlated with thiol concentration. The construction of new sites in the reaction process is a novel idea in the pursuit of multiple reaction sites, which will provide more effective tools for solving practical problems.