Structure Based Drug Design

In silico Modification of (1R, 2R, 3R, 5S)-(-)- Isopinocampheylamine as Inhibitors of M2 Proton Channel in Influenza A Virus Subtype H1N1, using the Molecular Docking Approach

by Arli Parikesit

Co-authored with Usman Sumo Friend Tambunan and Rahayu Harganingtyas

In 2009, swine flu attacked various countries in the world. World Health Organization (WHO) set influenza A H1N1 virus... more In 2009, swine flu attacked various countries in the world. World Health Organization (WHO) set influenza A H1N1 virus disease as a global pandemic on June 11, 2009. At least, there are approximately 18,449 people worldwide who died from this virus attack. Then, on August 10, 2010, WHO officially announced that the swine flu pandemic in the world has ended and changed into post-pandemic phase. The post-pandemic phase is the most appropriate phase to find an antiviral that can overcome the infection with this virus. The existing antivirals, amantadine and rimantadine, are reported to have experienced resistance. Therefore, it is necessary to find a new antiviral to replace amantadine and rimantadine as the M2 channel protein inhibitor of influenza A H1N1 virus. Later, it was reported that compound (1R, 2R, 3R, 5S)-(-)- isopinocampheylamine has the ability to inhibit channel M2 protein of influenza A H1N1 virus. This research modified (1R, 2R, 3R, 5S)-(-)- isopinocampheylamine in silico to obtain better inhibitors. Three inhibitors docking with standard and 52 inhibitor modifications were performed against the M2 protein channel and drug scan for modification inhibitors was also conducted. Docking results had the three best binding affinity of modification inhibitors and its potency of inhibition is much better than the standard ligands. Based on drug analysis scan, the modified inhibitor has good pharmacological properties which are indicated by the value of drug-likeness, drug score, oral bioavailability and toxicity.

HPV Bioinformatics: In Silico Detection, Drug Design and Prevention Agent Development

by Arli Parikesit

This is a book chapter. The book is edited by Dr Rajamanickam Rajkumar. Co-authored with Prof Usman S F Tambunan. Published in Intech 2012

Cervical Cancer is one of the leading cancers among women, especially in developing countries. Prevention and control... more Cervical Cancer is one of the leading cancers among women, especially in developing countries. Prevention and control are the most important public health strategies. Empowerment of women, education, "earlier" screening by affordable technologies like visual inspection, and treatment of precancers by cryotherapy/ LEEP are the most promising interventions to reduce the burden of cervical cancer.Dr Rajamanickam Rajkumar had the privilege of establishing a rural population based cancer registry in South India in 1996, as well as planning and implementing a large scale screening program for cervical cancer in 2000. The program was able to show a reduction in the incidence rate of cervical cancer by 25%, and reduction in mortality rate by 35%. This was the greatest inspiration for him to work on cerrvical cancer prevention, and he edited this book to inspire others to initiate such programs in developing countries. InTech - Open Access Publisher plays a major role in this crusade against cancer, and the authors have contributed to it very well.

Synthesis and biological evaluation of novel pyrazole derivatives with anticancer activity

by Camillo Rosano

MIBE acts as antagonist ligand of both estrogen receptor alpha and GPER in breast cancer cells

by Camillo Rosano

Structure-Based Approach for the Discovery of Novel Selective Estrogen Receptor Modulators

by Camillo Rosano

Estriol acts as a GPR30 antagonist in estrogen receptor-negative breast cancer cells

by Camillo Rosano

Molecular model of hexokinase binding to the outer mitochondrial membrane porin (VDAC1): Implication for the design of new cancer therapies

by Camillo Rosano

Structure–activity relationships of resveratrol and derivatives in breast cancer cells

by Camillo Rosano

In silico modification of suberoylanilide hydroxamic acid (SAHA) as potential inhibitor for class II histone deacetylase (HDAC)

by Arli Parikesit

Co-authored with Usman Sumo Friend Tambunan and Bramantya

Background: The cervical cancer is the second most prevalent cancer for the woman in the world. It is caused by the... more Background: The cervical cancer is the second most prevalent cancer for the woman in the world. It is caused by the oncogenic human papilloma virus (HPV). The inhibition activity of histone deacetylase (HDAC) is a potential strategy for cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is widely known as a low toxicity HDAC inhibitor. This research presents in silico SAHA modification by utilizing triazole, in order to obtain a better inhibitor. We conducted docking of the SAHA inhibitor and 12 modified versions to six class II HDAC enzymes, and then
proceeded with drug scanning of each one of them.
Results: The docking results show that the 12 modified inhibitors have much better binding affinity and inhibition potential than SAHA. Based on drug scan analysis, six of the modified inhibitors have robust pharmacological attributes, as revealed by drug likeness, drug score, oral bioavailability, and toxicity levels.
Conclusions: The binding affinity, free energy and drug scan screening of the best inhibitors have shown that 1c
and 2c modified inhibitors are the best ones to inhibit class II HDAC

Targeting the human DEAD-box polypeptide 3 (DDX3) RNA helicase as a novel strategy to inhibit viral replication

by Marco Radi

Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high... more Compounds currently used for the treatment of HIV-1 Infections are targeted to viral proteins. However, the high intrinsic mutation and replication rates of HIV-1 often lead to the emergence of drug resistant strains and consequent therapeutic failure. On this basis, cellular cofactors represent attractive new targets for HIV-1 chemotherapy, since targeting a cellular factor that is required for viral replication should help to overcome the problem of viral resistance. We and others have recently reported the identification of compounds suppressing HIV-1 replication by targeting the cellular DEAD-box helicase DDX3. These results provide a proof-of-principle for the feasibility of blocking HIV-1 infection by rendering the host cell environment less favorable for the virus. The rationale for such an approach and its implications in potentially overcoming the problem of drug resistance related to drugs targeting viral proteins will be discussed in the context of the known cellular functions of the DEAD-box helicase DDX3.

Regioselective one pot synthesis of 2-alkyl/aryl-4h-benzo[1,4]thiazine-3-one via microwave irradiation

by Omair Khan

Sukanta Kamila, Benjamin Koh, Omair Khan, Hongming Zhang, Edward R. Biehl. Regioselective one pot synthesis of 2-alkyl/aryl-4h-benzo[1,4]thiazine-3-one via microwave irradiation. Journal of Heterocyclic Chemistry, 43(6):16411646, 2006. doi:10.1002/jhet.5570430632

A series of 2-alkyl/aryl-4H-benzo[1,4]thiazine-3-ones have been synthesized by microwave irradiation of... more A series of 2-alkyl/aryl-4H-benzo[1,4]thiazine-3-ones have been synthesized by microwave irradiation of ethyl-2-bromo-2-alkyl/aryl acetate and 2-amino thiophenol in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene and N-methylpiperidine. All compounds were characterized by 1H NMR, 13C NMR and elemental analyses, and by X-ray crystallography in the case of 2-methyl-4H-benzo[1,4]thiazin-3-one.

Synthesis of 4,4-disubstituted-4h-benzo[d][1,3]oxathiin-2-ones, a new class of compounds

by Omair Khan

Sukanta Kamila, Omair Khan, Hongming Zhang, Edward Biehl. Synthesis of 4,4-disubstituted-4h-benzo[d][1,3]oxathiin-2-ones, a new class of compounds. Synthetic Communications, 36:14191429, 2006. doi:10.1080/00397910500522140

4,4-Dialkyl and 4,4-diaryl-4H-benzo[d][1,3]oxathiin-2-ones were synthesized by the reaction of... more 4,4-Dialkyl and 4,4-diaryl-4H-benzo[d][1,3]oxathiin-2-ones were synthesized by the reaction of 2-(mercapto-phenyl)-dialkyl- (or diaryl)-methanol with CDI in excellent yield. The 2-(mercaptophenyl)-dialkyl- (or diaryl)-methanols were prepared by the reaction of commercially available methylthiosalicylate with an appropriate alkyl or aryl Grignard reagent.

Probing the architecture of the Mycobacterium marinum arylamine N-acetyltransferase active site

by Areej Abuhammad

Role of tyrosine 131 in the active site of paAzoR1, an azoreductase with specificity for the inflammatory bowel disease prodrug balsalazide

by Areej Abuhammad

Improvement of the expression and purification of Mycobacterium tuberculosis arylamine N-acetyltransferase (TBNAT) a potential target for novel anti-tubercular …

by Areej Abuhammad

Analysis of [beta]-amino alcohols as inhibitors of the potential anti-tubercular target N-acetyltransferase

by Areej Abuhammad

Comparison of the Arylamine N-Acetyltransferase from Mycobacterium marinum and Mycobacterium tuberculosis

by Areej Abuhammad

A comparison of the binding of metal complexes to duplex and quaruplex DNA

by Kimberley Davis

Bayesian Inference Network Significantly Improves the Effectiveness of Similarity Searching Using Multiple 2D Fingerprints and Multiple Reference Structures

by Ammar Abdo

Published in "QSAR & Combinatorial Science Journal, Wiley, 2009"

Recent work in similarity searching have suggested that significant improvements in retrieval effectiveness can be... more Recent work in similarity searching have suggested that significant improvements in retrieval effectiveness can be achieved by combining results from multiple reference structures or multiple molecular descriptors. Recently, the Bayesian inference network model (BIN) has been introduced for performing molecular similarity searching using a single and multiple reference structures. One of the important characteristics of the inference network model is that it permits the combination of multiple reference structures and multiple molecular descriptors. This paper introduces an inference network model developed for molecular similarity searching that integrates into a single framework, multiple reference structures and multiple molecular descriptors. The inference network model of similarity, which was designed from this point of view, treats similarity searching as an evidential reasoning process where multiple sources of evidence about reference and compound content are combined to estimate similarity scores. Our results show that, the BIN with multiple descriptors is notably more effective than BIN with a single descriptor in searches for structurally diverse sets of actives molecules.

Conference Paper: Interaction of Antiparasitic Peptides Active against African Sleeping Sickness with cell membrane models

by Claudius D'Silva

7th Brazilian MRS meeting, Guaruja, Sao Paulo, Brazil. Oct 2nd, 2008