Novel 5-pyridinyl-1,2,4-triazoles were designed as dual inhibitors of histone deacetylase 2 (HDAC2) and
focal adhesion kinase (FAK). Compounds 5d, 6a, 7c, and 11c were determined as potential inhibitors of
both HDAC2 (IC50 ¼ 0.09e1.40 mM) and FAK (IC50 ¼ 12.59e36.11 nM); 6a revealed the highest activity
with IC50 values of 0.09 mM and 12.59 nM for HDAC2 and FAK, respectively. Compound 6a was superior to
reference drugs vorinostat and valproic acid in its ability to inhibit growth/proliferation of A-498 and
Caki-1 renal cancer cells. Further investigation proved that 6a strongly arrests the cell cycle at the G2/M
phase and triggers apoptosis in both A-498 and Caki-1 cells. Moreover, the enhanced Akt activity that is
observed upon chronic application of HDAC inhibitors was effectively suppressed by the dual HDAC2/FAK
inhibitor. Finally, the high potency and selectivity of 6a towards HDAC2 and FAK proteins were rationalized
by molecular docking. Taken together, these findings highlight the potential of 6a as a promising
dual-acting HDAC2/FAK inhibitor that could benefit from further optimization.

Avanafil (AVN) is a new selective phosphodiesterase-5 (PDE-5) inhibitor, which is used as an oral treatment of
erectile dysfunction. Coadministration of avanafil (AVN) with some antihypertensive drugs especially in elderly
patients is a very common case. Nimodipine (NIM) is one of these hypotensive drugs that are commonly
coadministered. Synergistic hypotension effect as a result of AVN and NIM coadministration is expected;
therefore, it is mandatory to study the possible pharmacokinetic interaction between them. The main aim of the
current work is to develop a simple, sensitive, and selective electrochemical method for simultaneous determination of AVN and NIM in human serum samples. Nickel oxide nanoparticles/poly(sulfanilamide) film was
used as a new electrochemical modifier, which is electrodeposited on the surface of pencil graphite electrode
(PGE) to improve its electrochemical properties. The best resolution between the two studied drugs was achieved
by using Britton-Robinson buffer (BRB) at pH 3.0 producing two peaks at 1.45 V and 0.80 V for AVN and NIM,
respectively. Furthermore, cyclic voltammetry was utilized for the first time to study the oxidation behavior of
AVN and NIM and a plausible oxidation mechanism was suggested for both of them. The proposed square wave
voltammetric method was successfully applied for trace quantification of AVN and NIM in real human serum
samples with detection and quantitation limits of 0.037 and 0.10 μmol L- 1 for AVN and 0.32 and 0.98 μmol L- 1
for NIM, respectively. Moreover, the suggested approach was effectively implemented to investigate the possible
pharmacokinetic interaction between AVN and NIM in serum samples of heathy human male volunteers. It was
found from the pharmacokinetic parameters calculated for AVN when administered alone or in presence of NIM
that there is a significant increase of serum concentration of AVN, when it is coadminstered with NIM, which
stresses the importance of dose adjustment of AVN when coadministered with NIM.

Diatoms are unicellular photosynthetic algae enclosed in 3-dimensional (3D) nano patterned silica cell walls called frustules. They are made of intricate porous biosilica that feature unique properties including high specific surface area, biocompatibility, tailorable surface chemistry, thermal stability and high mechanical and chemical resistance. Additionally, the facile cultivation of diatoms in artificial environment, and the abundant availability of diatom frustules as fossilized mineral (diatomite) from mining industry confirm the benefits of using diatoms as an alternative to synthetic porous silica for a broad range of applications. These attributes make them a remarkable candidate for a variety of biomedical applications including drug delivery. In this chapter, the potential use of diatoms, as micro- and nano frustules (i.e., silica) or reduced to silicon replicas, for biomedical applications with emphasis on their use as drug carriers is described. The selected aspects on the preparation of diatom frustules, in addition to surface chemical functionalization, drug loading, their cellular uptake as well as capability to transport therapeutic molecules inside cells are presented