Sarita Roy

Mahanine, A DNA Minor Groove Binding Agent Exerts Cellular Cytotoxicity with Involvement of C-7-OH and −NH Functional Groups

Mahanine, a carbazole alkaloid is a potent anticancer molecule. To recognize the structure-activity correlation, mahanine was chemically modified. Antiproliferative activity of these derivatives was determined in 19 cancer cell lines from 7 different origins. Mahanine showed enhanced apoptosis compared to dehydroxy-mahanine-treated cells, indicating significant contribution of the C-7-OH group. O-Methylated-mahanine and N-methylated dehydroxy-mahanine-treated cells exhibited apoptosis only at higher concentrations, suggesting additional contribution of 9-NH group. Using biophysical techniques, we demonstrated that mahanine interacts with DNA through strong association with phosphate backbone compared to other derivatives but is unable to induce any conformational change in DNA, hence suggesting the possibility of being a minor groove binder. This was corroborated by molecular modeling and isothermal titration calorimetry studies. Taken together, the results of the current study represent the first evidence of involvement of C-7-OH and 9-NH group of mahanine for its cytotoxicity and its minor groove binding ability with DNA.

Chirality sensitive binding of tryptophan enantiomers with pristine single wall carbon nanotubes

We report the differential binding nature of pristine single wall carbon nanotubes (SWNTs) with tryptophan enantiomers. The differential co-operative response between the pristine SWNTs (topologically chiral) and L- and D-tryptophan (geometrically chiral) provides the insight that geometrical chirality itself manifests with topological chirality in a complex way.

Induced chirality in single walled carbon nanotube based self-assembly

Chirality is an important determinant of the optical and electronic properties of single walled carbon nanotubes (SWNTs). Pristine zigzag SWNTs have been functionalized with lipids by a solid state functionalization process. Neither the lipids nor the SWNTs show a circular dichroism (CD) signal prior to functionalization. Upon functionalization, a change in the joint density of electronic states occurs which is reflected by a three-peak G′ band profile and the emergence of a CD signal. A molecular mechanism for the emergent CD signal associated with this lipid-specific self-assembly is described.

Platelet responsiveness to yohimbine hydrochloride and MRS2179 in the context of the interaction between collagen and epinephrine in acute coronary syndrome

Acute coronary syndrome (ACS) covers a spectrum of clinical conditions ranging from unstable angina, Non-ST segment elevation myocardial infarction (NSTEMI), or ST segment elevation myocardial infarction (STEMI). This study encompasses patients with acute coronary syndrome, who were receiving the dual antiplatelet therapy of aspirin and clopidogrel. The focus of the study was to gain insight into the role of selective P2Y1 antagonism using MRS2179 in such cases as well as its effects, if any, on collagen-epinephrine interaction. All the cases showed greater potency of inhibition of the interaction when yohimbine hydrochloride (YH), a blocker of alpha2A-adrenoreceptor, was used compared to MRS2179, a P2Y1 antagonist, although there was variability in responsiveness to the antiplatelet drugs. These findings indicate that alpha2A-adrenoreceptors of platelets in this group play a major role in precipitating the interactive effect of collagen and epinephrine. The dose-response effect as studied by platelet aggregometry showed that the required molar concentration to block the interactive effect in the case of YH was less than that of MRS2179. Hence, it is postulated that although there may be an impairment of collagen-induced aggregation by MRS2179, the interactive effect of collagen-epinephrine may not be impaired by MRS2179 as efficaciously as YH.

Cellular response to chirality and amplified chirality

In this paper we have explored how cancer cell line U87MG responds to drug penicillamine (PA) with reciprocal enantiomeric identities (i.e.l, d-forms). As nano-conjugation leads to amplification of chirality, cellular response to respective chiral forms is studied in the presence and absence of nano-conjugation. The l, d-forms of the drug (penicillamine) and their silver nanoparticle conjugated forms are used and characterized by circular dichroism and fourier transform infrared spectroscopy. We report that cells discriminate between the chiral forms through various mechanisms e.g. by altering mitochondrial membrane potential and selected elements of the caspase pathway. The striking feature which we would like to report is that chirality and the amplified chirality induced reciprocal responses may be dissimilar and even reciprocal. The work shows that the cellular response to geometrical chirality is an evolved concept and an amplified chirality by processes like nano-conjugation may be translated into an altered message in the cell.

Design of Heat Shock-Resistant Surfaces to Prevent Protein Aggregation: Enhanced Chaperone Activity of Immobilized α-Crystallin

α-Crystallin is a multimeric protein belonging to the family of small heat shock proteins, which function as molecular chaperones by resisting heat and oxidative stress induced aggregation of other proteins. We immobilized α-Crystallin on a self-assembled monolayer on glass surface and studied its activity in terms of the prevention of aggregation of aldolase. We discovered that playing with grafted protein density led to interesting variations in the chaperone activity of immobilized α-Crystallin. This result is in accordance with the hypothesis that dynamicity of subunits plays a vital role in the functioning of α-Crystallin and might be able to throw light on the structure-activity relationship. We showed that the chaperone activity of a certain number of immobilized α-Crystallins was superior compared to a solution containing an equivalent number of the protein and 10 times the number of the protein at temperatures >60 °C. The α-Crystallin grafted surfaces retained activity on reuse. This could also lead to the design of potent heat-shock resistant surfaces that can find wide applications in storage and shipping of protein based biopharmaceuticals.

Cancer research: India meets the West.

What can be more befitting than bringing a large number of cancer research experts from various parts of the globe to discuss recent advancements in complex cellular signaling network and cancer in a city that has more than 300-year-old rich history of culture and produced all nobel laureates from India. This meeting was organized by CSIR-IICB, which brought together several scientists from USA, UK, Canada, Germany, Japan, South Korea, Singapore, Italy and Australia, as well as a very large number of scientists from all over India to discuss emerging areas such as cancer cell signaling, signal networks, cell survival and novel or traditional therapeutic approaches to treat different cancers. The meeting was particularly enriched with the presence of large contingent of PhD students and research scholars from all over India, who presented their latest research findings in the area of cancer through more than 100 posters and 20 oral presentations. The meeting was as a part of the 30th Annual Convention of the Indian Association for Cancer Research (IACR) a premier body that promotes cancer research, education and awareness in India. IACR was founded in 1981 and is now a leading body of cancer research in India. It continues to attract people from diverse areas with a common interest in cancer.