Murugesan Sankaranarayanan

Synthesis and in-vitro anti-leishmanial activity of (4-arylpiperazin-1-yl)(1-(thiophen-2-yl)-9H-pyrido[3,4-b]indol-3-yl)methanone derivatives

In the present study, we have reported synthesis and biological evaluation of a series of fifteen 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole derivatives against both promastigotes and amastigotes of Leishmania parasites responsible for visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis. Among these reported analogues, compounds 7b, 7c, 7f, 7g, 7i, 7j, 7m, 7o displayed potent activity (15.55, 7.70, 7.00, 3.80, 14.10, 9.25, 3.10, 4.85μM, respectively) against L. donovani promastigotes than standard drugs miltefosine (15.70μM) and pentamidine (32.70μM) with good selectivity index. In further, in-vitro evaluation against amastigote forms, two compounds 7g (8.80μM) and 7i (7.50μM) showed significant inhibition of L. donovani amastigotes. Standard drug amphotericin B is also used as control to compare inhibition potency of compounds against both promastigote (0.24μM) and amastigote (0.05μM) forms.

Synthesis, characterization, POM analysis and antifungal activity of novel heterocyclic chalcone derivatives containing acylated pyrazole

A series of heterocyclic chalcone derivatives (4a–h) were synthesized and characterized by IR, 1H and 13C NMR as well as MS. All the synthesized compounds were evaluated for their antifungal activity on Candida albicans and Aspergillus niger. The assay revealed that compounds 3d and 4f showed significant activity against both tested fungal strains. POM analyses showed that the compounds are highly lipophyllic but present a potential bioactivity. Moreover, they have no NH–O or N–HO intramoleculcular interaction which is a crucial parameter controlling solubility of compounds possessing these encouraging pharmaceutical properties. This series gives us an important lesson in drug design: We should take the balance of hydrosolubility/lipophilicity into consideration. POM analyses were in agreement with the idea of coexistence of two combined antifungal N,O and O,S-pharmacophore sites for series 4a–h. On the other hand, two coexistents and identical N,Cl-pharmacophore sites have been identified for Fluconazole.Graphical Abstract

Design, synthesis and anti-HIV-1 RT evaluation of 2-(benzyl(4-chlorophenyl)amino)-1-(piperazin-1-yl)ethanone derivatives.

In this study, using molecular hybridization approach, fourteen novel 2-(benzyl(4-chlorophenyl)amino)-1-(piperazin-1-yl)ethanone derivatives (7a-n) were designed as inhibitor of HIV-1 RT. The binding affinity of the designed compounds with HIV-1 RT as well as their drug-likeness behavior was predicted using in-silico studies. All the designed compounds were synthesized, characterized and in-vitro evaluated for HIV-1 RT inhibitory activity, in which tested compounds displayed significant to weak potency against the selected target. Moreover, best active compounds of the series, 7k and 7m inhibited the activity of RT with IC50 values 14.18 and 12.26μM respectively. Structure Activity Relationship (SAR) studies were also performed in order to predict the influence of substitution pattern on the RT inhibitory potency. Anti-HIV-1 and cytotoxicity studies of best five RT inhibitor (7a, 7d, 7k, 7L and 7m) revealed that, except compound 7d other compounds retained significant anti-HIV-1 potency with good safety index. Best scoring pose of compound 7m was analysed in order to predict its putative binding mode with wild HIV-1 RT.

Synthesis and study of anti-HIV-1 RT activity of 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives

In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC50≤25µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50 values 8.62 and 6.87µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.

Synthesis and activity of benzopiperidine, benzopyridine and phenyl piperazine based compounds against Leishmania infantum

In the present study, anti-leishmanial evaluation of twenty four structurally diverse compounds based on benzopiperidine, benzopyridine and phenylpiperazine nucleuses against Leishmania infantum has been reported. Cytotoxicity studies of all the compounds were performed on murine non-infected splenocytes. Tested compounds exhibited weak to potent activity against promastigote (IC50 3.21 ± 1.40 to >100 μM) as well as amastigote (IC50 6.84 ± 2.5 to 92.47 ± 17.61 μM) forms of tested strains. Moreover, two compounds F13 and F15 exhibited potent activity (IC50 < 10 μM) against both forms of the parasite with selectivity index ranges from 11.40 to 22.10. Overall, the current study afforded few hits with novel anti-leishmanial activity in low micromolar concentration, further hit optimization studies can be performed to get more potent candidates against the selected species of parasite.

Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential anti-HIV-1 agents

In the current study, twenty-two compounds based upon 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one nucleus were designed, synthesized and in vitro evaluated for HIV-1 RT inhibition and anti-HIV-1 activity. Compounds 3d, 5c and 5e demonstrated encouraging potency against RT enzyme as well as HIV-1 in low micromolar to nanomolar concentration with good to excellent safety index. Structure activity relationship studies revealed that halogens such as bromo or chloro at 5th the position of oxindole ring remarkably enhanced the potency against RT. Moreover, methoxy or chloro groups at the ortho position of phenyl ring also significantly favored RT inhibition activity. Seven compounds (3b, 3c, 3d, 3e, 5b, 5c and 5e) with better anti-HIV-1 potency were tested against the mutant HIV-1K103N strain. The putative binding mode, as well as interaction patterns of the best active compound 5c with wild HIV-1 RT were studied via docking studies.

Design, Graph Theoretical Analysis and Insilico Modeling of Dunaliella bardawil Biomass Encapsulated N-Succinyl Chitosan Nanoparticles for Enhanced Anticancer Activity

PURPOSE To investigate N-succinyl chitosan nanoparticles (NSC NPs) encapsulation with Dunaliella bardawil (D. bardawil) biomass for high utilization enhanced effectiveness and least side effects for anticancer activity. METHODS The potential bioactive compounds from D. bardawil biomass were encapsulated NSC NPs by ionotropic gelation method and to characterize its molecular shape, particle size, stability and polydispersity index using FTIR, XRD, SEM, TEM and Zetasize Nano analyzer. Signaling pathway analysis, molecular docking study and in vitro anticancer screening were performed on chosen H-RasP21, 721P and liver cancer cell lines (HepG2), respectively. RESULTS The D. bardawil biomass majorly contains 6 bioactive compounds such as β-carotene, lutein, zeaxanthin, phytoene, canthaxanthin, and phytofluene were identified by LC-MS. The D. bardawil biomass encapsulated NSC NPs showed an average particle size of 80±5.6 nm in spherical shape, crystalline nature, zeta potential of -32±2.7 mV and polydispersity index of 0.51±0.02. Interestingly, the identified target using graph theoretical signaling pathway analysis and molecular docking study showed strong interaction of NSC NPs in binding pockets of H-RasP21 protooncogene. At 50μg/mL, NPs displayed 95.60% cytotoxicity in HepG2 cell line. The apoptotic cell cycle analysis showed cell death for 24 h and 48 h representing 13.13% and 47.04%, respectively. CONCLUSION The highly cross-linked, biocompatible, biodegradable, nontoxic NSC NPs promising carrier for delivery of bioactive molecules present in the D. bardawil biomass was found to be actively involved in deregulation of cellular growth in targeted cancer cells. Thus active NPs serve as a novel nanodrug to enhance the controlled; site specific drug delivery in the management of cancer.