Design, Synthesis, Anticancer Evaluation, and Molecular Docking Studies of Novel Benzoxazole Linked 1,3,4-Oxadiazoles.

BACKGROUND: Cancer disease is a serious concern globally. Global cancer occurrence is steadily increasing every year. There is always a persistent need to develop new anticancer drugs with reduced side effects or that act synergistically with the existing chemotherapeutics. OBJECTIVE: Benzoxazoles are fused bicyclic nitrogen and oxygen-containing heterocyclic compounds and are considered biologically privileged scaffolds. We designed a synthetic route to link the benzoxazoles with oxadiazole,s resulting in a better pharmacophore for anticancer activity. METHODS: A series of novel amide derivatives of benzoxazole linked 1,3,4-oxadiazoles (10 a-j) were synthesized and characterized by 1H NMR, 13C NMR, and mass spectroscopic techniques. The biological properties of the compounds were screened in vitro against four different tumor cell lines. RESULTS: The results suggest that the compound 10b having 3,4,5-trimethoxy substitution on the phenyl ring exhibited potent anticancer activity in three cell lines (A549 = 0.13 ± 0.014 µM, MCF-7 = 0.10 ± 0.013 µM and HT-29 = 0.22 ± 0.017 µM). Notably, among the synthesized derivatives, compounds 10b, 10c, 10f, 10g, and 10i exhibited potent anticancer activity than the control, with IC50 values in the range from 0.11 ± 0.02 to 0.93 ± 0.034 µM. Molecular docking simulation results showed that compounds were stabilized by hydrogen bond and π-π interactions with the protein. CONCLUSION: The molecules showed comparable binding affinities with standard Combretastatin-A4. The present research work is in a preliminary phase and needs further studies to take the synthesized compounds to the next level in the cancer research field.

RP-HPLC-UV method development and validation for simultaneous determination of terbutaline sulphate, ambroxol HCl and guaifenesin in pure and dosage forms.

OBJECTIVE: The objective of the present work was to develop and validate a simple, sensitive, rapid and stable reverse-phase high performance liquid chromatography (RP-HPLC) method for a combination of Terbutaline sulphate (TSL), Ambroxol hydrochloride (AML) and Guaifenesin (GFN). METHOD: The combination of these drugs was analyzed by using Shimadzu LC 2010 CHT high performance liquid chromatography (HPLC). Successful separation was achieved by isocratic elution on a reverse-phase C18 column (sun fire) (250mm, 4.6mm, 5µ), using a mobile phase consisting of buffer: acetonitrile in the ratio 80: 20 (buffer - 0.1% v/v triethyleamine pH-3.0) followed by 1.0mL/min flow rate. The wavelength of detection was at 220nm. RESULT: The chromatographic retention times were consistent at 3.0, 10.5 and 13.8minutes for TSL, AML and GFN respectively. For these three compounds, the lower limit of detection was 1.0, 1.25, and 1.5µg/mL and lower limit of quantification was 3.3, 4.1 and 5.0µg/mL respectively. The linearity concentrations established for TSL, AML and GFN were 1.0-7.0, 1.5-7.5 and 4.0-14.0µg/mL respectively. The correlation coefficients for all the drugs were found to be greater than 0.999. The relative standard deviation of inter- and intra-day were less than 2.0%. CONCLUSION: This method provides a necessary tool for quantification of the selected drugs for their assay. The proposed method is simple, accurate, reproducible and applied successfully to analyze three compounds in pure as well dosage form.

Cationic surfactant-based colorimetric detection of Plasmodium lactate dehydrogenase, a biomarker for malaria, using the specific DNA aptamer.

A simple, sensitive, and selective colorimetric biosensor for the detection of the malarial biomarkers Plasmodium vivax lactate dehydrogenase (PvLDH) and Plasmodium falciparum LDH (PfLDH) was demonstrated using the pL1 aptamer as the recognition element and gold nanoparticles (AuNPs) as probes. The proposed method is based on the aggregation of AuNPs using hexadecyltrimethylammonium bromide (CTAB). The AuNPs exhibited a sensitive color change from red to blue, which could be seen directly with the naked eye and was monitored using UV-visible absorption spectroscopy and transmission electron microscopy (TEM). The reaction conditions were optimized to obtain the maximum color intensity. PvLDH and PfLDH were discernible with a detection limit of 1.25 pM and 2.94 pM, respectively. The applicability of the proposed biosensor was also examined in commercially available human serum.

A colorimetric aptasensor for the diagnosis of malaria based on cationic polymers and gold nanoparticles.

Malaria, a major burden of disease caused by parasites of the genus Plasmodium, is widely spread in tropical and subtropical regions. Here, we have successfully developed a diagnostic technique for malaria. The proposed method is based on the interaction among the Plasmodium lactate dehydrogenase (pLDH), which is a biomarker for malaria, and pL1 aptamer against Plasmodium vivax lactate dehydrogenase (PvLDH) and Plasmodium falciparum lactate dehydrogenase (PfLDH). In addition, the cationic polymers, poly(diallyldimethylammonium chloride) (PDDA) and poly(allylamine hydrochloride) (PAH), aggregate gold nanoparticles (AuNPs) that should be possible to observe the change in color from red to blue, which depends on the concentration of pLDH. Using this aptasensor, pLDH proteins were successfully detected with low detection limits. Moreover, the specificity test proved that the aptasenor is very specific in targeting proteins over other interfering proteins. In addition, the pLDH from infected blood samples of the two main species of malaria were also detected. The limits of detection for P. vivax were determined as 80 parasites/µl for PDDA and 74 parasites/µl for PAH. The aptasenor has great advantages that can simply and rapidly diagnose malaria. Thus, the developed aptasensor for detection of pLDH can offer an effective and sensitive diagnosis of malaria.

Mechanism of interaction between human serum albumin and N-alkyl phenothiazines studied using spectroscopic methods.

The binding characteristics of human serum albumin (HSA) with N-alkyl phenothiazines derivatives (NAP) viz., levomepromazine monomaleate (LMM) and propericiazine (PPC) have been studied by employing fluorescence, absorption, circular dichroism and FT-IR techniques. The Stern-Volmer quenching constant, K(SV) values were found to decrease with increase in temperature thereby indicating the presence of static quenching mechanism in the interactions of NAP with HSA. The number of binding sites, n and the binding constant, K were noticed to be, respectively, 1.11 and (5.188+/-0.034)x10(4) M(-1) for LMM and 1.06 and (4.436+/-0.066)x10(4) M(-1) for PPC at 298 K. The negative value of enthalpy change and positive value of entropy change in the present study indicated that the hydrophobic forces played a major role in the binding of NAP to HSA. The circular dichroism and FT-IR spectral data revealed the conformational changes in the structure of protein upon its interaction with NAP. The binding distances and the energy transfer efficiency between NAP and protein were determined based on Förster's theory of energy transfer. The decreased binding constants of HAS-LMM and HAS-PPC systems in presence of common ions indicated the availability of higher concentration of free drug in plasma.

In vitro study on the binding of anti-coagulant vitamin to bovine serum albumin and the influence of toxic ions and common ions on binding.

The mechanism of binding of vitamin K(3) (VK(3)) with bovine serum albumin (BSA) was investigated by fluorescence, absorption and circular dichroism (CD) techniques under physiological conditions. The analysis of fluorescence data indicated the presence of static quenching mechanism in the binding. Various binding parameters have been evaluated. Thermodynamic parameters, the standard enthalpy change, DeltaH(0) and the standard entropy change, DeltaS(0) were observed to be -164.09 kJ mol(-1) and -465.08 J mol(-1)K, respectively. The quantitative analysis of CD spectra confirmed the change in secondary structure of the protein upon interaction with VK(3). The binding average distance, r between the donor (BSA) and acceptor (VK(3)) was determined based on the Förster's theory and it was found to be 3.3 nm. The effects of toxic ions and common ions on VK(3)-BSA system were also investigated.

Study of the interaction between doxepin hydrochloride and bovine serum albumin by spectroscopic techniques.

The binding of doxepin hydrochloride (DH) to bovine serum albumin (BSA) was investigated by spectroscopic (fluorescence, UV-vis absorption and circular dichroism) techniques. The binding parameters have been evaluated by fluorescence quenching method. The thermodynamic parameters, Delta H major, Delta S major, and Delta G major calculated at different temperatures indicated that the hydrogen bond and hydrophobic forces played a major role in the interaction of DH with BSA. Based on the Förster's theory of non-radiation energy transfer, the binding average distance, r between the donor (BSA) and acceptor (DH) was evaluated and found to be 2.7 nm. Spectral results observed showed that the binding of DH to BSA induced conformational changes in BSA. The effect of common ions on the binding of DH to BSA was also examined.