A novel naproxen derivative capable of displaying anti-cancer and anti-migratory properties against human breast cancer cells

BACKGROUND: Increasingly, the role of chronic inflammation and its mediators in tumor generation and progression is gaining importance in the field of cancer research. In this context, candidature of non steroidal anti-inflammatory drugs (NSAIDs) as potential anti-tumor therapeutic agent is being evaluated globally. In the present study we have evaluated the anti-cancer effect of a series of newly synthesized naproxen derivatives on human breast cancer cell lines. METHODS: MCF-7 (poorly invasive) and MDA-MB-231 (highly invasive) cells were treated with different concentrations of naproxen sodium and its derivatives in vitro, and the underlying mechanism of action was monitored by employing studies related to induction of apoptosis, activation of caspases, cell-cycle progression, synthesis of PGE(2) and cellular migration. RESULTS: After a preliminary screening using MCF-7 and MDA-MB-231 cells, it was evident that naproxen derivative 4 has a better killing property compared to its parent compound naproxen sodium (NS). On further investigation, it was apparent that the observed growth inhibitory activity on MDA-MB-231 cells after treatment with 4, was not due to cell cycle arrest but due to an early induction of apoptosis and subsequent induction of caspases 3 and 9. Derivative 4 could also inhibit COX activity in MDA-MB-231 cells as evidenced by reduction in prostaglandin E2 secretion. Moreover, 4 was capable of delaying the overall migration rate of MDA-MB-231 cells in vitro. CONCLUSION: In this study we report that a naproxen-derivative (4) has powerful anti-inflammatory and anti-tumor properties as it induces appreciable amount of apoptosis in breast cancer cell line, and can also delay migration of cancer cells (MDA-MB-231) which would in turn delay cancer cell invasion and formation of secondary tumours in primary breast cancer patients. Thus, we propose that 4 is worthy of further investigation due to its potential as a therapeutic agent in anti-tumor treatment regimen

Missense mutations in SARS-CoV2 genomes from Indian patients

As on May 24, 2020, in the NCBI database, there are complete genome sequences of SARS-CoV2 from 128 Indian patients. In this present study, variations among these genomes based on missense mutations are accounted and thereby some key findings with some hypotheses are made. These mutations across various genes of these genomes show a wide genetic variations in sequence and rapid evolution of SARS-CoV2 virus

Cetirizine derived supramolecular topical gel in action: Rational design, characterization and in vivo self-delivery application in treating skin allergy in mice

A conventional drug delivery system requires a delivery vehicle which often faces various problems such as inefficient drug loading into the delivery vehicle and its release, cytotoxicity and biodegradability of the delivery vehicle, etc., whereas a supramolecular gel based self-delivery system delivers a gelator drug at the target site without using any vehicle thereby getting rid of such problems. Here, a simple salt formation strategy has been employed to convert a well known anti-allergic drug (cetirizine) to a supramolecular gelator for the purpose of making a topical gel for in vivo self-delivery applications. The salt of cetirizine and tyramine (salt 3) displays excellent gelation properties in methylsalicylate/menthol. The gels are characterised by electron microscopy, and table top- and dynamic rheology. The gelator salt 3 displays excellent physiological stability in phosphate buffer saline (PBS) and it is biocompatible in mouse macrophage RAW 264.7 and mouse myoblast C2C12 cell lines. A methylsalicylate/menthol topical gel of salt 3 is successfully self-delivered in treating the 2,4-dinitrochlorobenzene (DNCB)-induced allergic skin condition in mice

β-amino acid and amino-alcohol conjugation of a Nonsteroidal Anti-Inflammatory Drug (NSAID) imparts hydrogelation displaying remarkable biostability, biocompatibility, and anti-inflammatory properties

A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with β-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable ¹H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure–property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E2 (PGE2) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns)

Designing a simple organic salt-based supramolecular topical gel capable of displaying in vivo self-delivery application

The supramolecular synthon approach has been exploited to design simple salt-based supramolecular gelators derived from a non-steroidal anti-inflammatory drug (NSAID) – naproxen; one such biocompatible anti-inflammatory gelator salt was converted into a topical gel that showed excellent in vivo self-delivery application in treating imiquimod (IMQ)-induced skin inflammation in mice

Dynamics of Gene Silencing in a Live Cell: Stochastic Resonance

Binding of a specific siRNA to the target mRNA in a live cell (human breast cancer cell, MCF-7) is studied by confocal microscopy. The specific siRNA (labeled with a fluorophore, alexa 488) exhibits much higher intensity of fluorescence in the bound state than in the free (unbound) state. It is observed that repeated unbinding and rebinding of siRNA (to target mRNA) occur before gene silencing. 16 273 on-time periods (residence or dwell time of siRNA in bound form) are detected. They follow a strikingly simple pattern. All of the on-time periods are odd-integral multiples of 5.5 ± 0.05 ms. This is ascribed to stochastic resonance

β‑Amino Acid and Amino-Alcohol Conjugation of a Nonsteroidal Anti-Inflammatory Drug (NSAID) Imparts Hydrogelation Displaying Remarkable Biostability, Biocompatibility, and Anti-Inflammatory Properties

A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with β-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable ¹H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure–property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E₂ (PGE₂) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns)

β‑Amino Acid and Amino-Alcohol Conjugation of a Nonsteroidal Anti-Inflammatory Drug (NSAID) Imparts Hydrogelation Displaying Remarkable Biostability, Biocompatibility, and Anti-Inflammatory Properties

A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with β-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable ¹H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure–property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E₂ (PGE₂) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns)

β‑Amino Acid and Amino-Alcohol Conjugation of a Nonsteroidal Anti-Inflammatory Drug (NSAID) Imparts Hydrogelation Displaying Remarkable Biostability, Biocompatibility, and Anti-Inflammatory Properties

A well-known nonsteroidal anti-inflammatory drug (NSAID), namely, naproxen (Np), was conjugated with β-alanine and various combinations of amino alcohols and l-alanine. Quite a few bioconjugates, thus synthesized, were capable of gelling pure water, NaCl solution (0.9 wt %), and phosphate-buffered saline (PBS) (pH 7.4). The hydrogels were characterized by rheology and electron microscopy. Hydrogelation was probed by FT-IR and temperature-variable ¹H NMR studies. Single-crystal X-ray diffraction (SXRD) of a nonhydrogelator and a hydrogelator in the series established a useful structure–property (gelation) correlation. MTT assay of the hydrogelators in the mouse macrophage RAW 264.7 cell line showed excellent biocompatibility. The prostaglandin E₂ (PGE₂) assay of the hydrogelators revealed their anti-inflammatory response, which was comparable to that of the parent NSAID naproxen sodium (Ns)

Mathematical Characterization of Protein Sequences Using Patterns as Chemical Group Combinations of Amino Acids

<div><p>Comparison of amino acid sequence similarity is the fundamental concept behind the protein phylogenetic tree formation. By virtue of this method, we can explain the evolutionary relationships, but further explanations are not possible unless sequences are studied through the chemical nature of individual amino acids. Here we develop a new methodology to characterize the protein sequences on the basis of the chemical nature of the amino acids. We design various algorithms for studying the variation of chemical group transitions and various chemical group combinations as patterns in the protein sequences. The amino acid sequence of conventional myosin II head domain of 14 family members are taken to illustrate this new approach. We find two blocks of maximum length 6 aa as ‘FPKATD’ and ‘Y/FTNEKL’ without repeating the same chemical nature and one block of maximum length 20 aa with the repetition of chemical nature which are common among all 14 members. We also check commonality with another motor protein sub-family kinesin, KIF1A. Based on our analysis we find a common block of length 8 aa both in myosin II and KIF1A. This motif is located in the neck linker region which could be responsible for the generation of mechanical force, enabling us to find the unique blocks which remain chemically conserved across the family. We also validate our methodology with different protein families such as MYOI, Myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), Na⁺/K⁺-ATPase and Ca²⁺-ATPase. Altogether, our studies provide a new methodology for investigating the conserved amino acids’ pattern in different proteins.</p></div