Sadanandan E Velu

Sadanandan E Velu
University of Alabama at Birmingham | UAB · Department of Chemistry

PhD

About

123
Publications
8,846
Reads
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1,775
Citations
Additional affiliations
July 2020 - present
University of Alabama at Birmingham
Position
  • Professor
Description
  • Foundations of Organic Chemistry (CH701) Natural Product Chemistry (CH772) Organic Reactions and Synthesis (CH732), Medicinal Chemistry & Drug Discovery (CH771) Organic Chemistry I (CH235) Organic Chemistry II (CH237) Senior Research (CH497)
August 2010 - July 2020
University of Alabama at Birmingham
Position
  • Professor (Associate)
August 2004 - August 2010
University of Alabama at Birmingham
Position
  • Professor (Assistant)
Education
June 1986 - April 1992
University of Madras
Field of study
  • Organic Chemistry
June 1983 - April 1985
University of Calicut
Field of study
  • Chemistry
June 1980 - May 1983
University of Calicut
Field of study
  • Chemistry

Publications

Publications (123)
Article
Full-text available
The production of noncanonical mRNA transcripts is associated with cell transformation. Driven by our previous findings on the sensitivity of T cell acute lymphoblastic leukemia (T-ALL) cells to SF3B1 inhibitors, we identified that SF3B1 inhibition blocks T-ALL growth in vivo with no notable associated toxicity. We also revealed protein stabilizati...
Article
Additional prognostic and therapeutic biomarkers effective across different histological types of sarcoma are needed. Herein we evaluate expression of TAZ and YAP, the p53-MDM2 axis, and RABL6A, a novel oncoprotein with potential ties to both pathways, in sarcomas of different histological types. Immunohistochemical staining of a tissue microarray...
Article
Full-text available
Voltage-gated sodium (NaV) channels, initially characterized in excitable cells, have been shown to be aberrantly expressed in non-excitable cancer tissues and cells from epithelial origins such as in breast, lung, prostate, colon, cervix, while they are not expressed in cognate non-cancer tissues. Their activity was demonstrated to promote aggress...
Article
Full-text available
The oncogenic human herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) are the causative agents of multiple malignancies. A hallmark of herpesviruses is their biphasic life cycle consisting of latent and lytic infection. In this study, we identified that cellular nonsense-mediated decay (NMD), an evolutionaril...
Article
Dental caries is a bacterial infectious disease characterized by demineralization of the tooth enamel. Treatment of this disease with conventional antibiotics is largely ineffective as the cariogenic bacteria form tenacious biofilms that are resistant to such treatments. The main etiological agent for dental caries is the bacterium Streptococcus mu...
Article
Full-text available
In an effort to discover viable systemic chemotherapeutic agents for neuroendocrine tumors (NETs), we screened a small library of 18 drug-like compounds obtained from the Velu lab against pulmonary (H727) and thyroid (MZ-CRC-1 and TT) neuroendocrine tumor-derived cell lines. Two potent lead compounds (DHN-II-84 and DHN-III-14) identified from this...
Article
Full-text available
Non-melanoma skin cancer is one of the major ailments in the United States. Effective drugs that can cure skin cancers are limited. Moreover, the available drugs have toxic side effects. Therefore, skin cancer drugs with less toxic side effects are urgently needed. To achieve this goal, we focused our work on identifying potent lead compounds from...
Conference Paper
Hepatocellular carcinoma (HCC) poses a major public health problem worldwide and novel, effective therapeutic approaches for this devastating disease are urgently needed. The overexpression or activation of the MDM2 oncogene frequently occurs in HCC and is linked to cancer growth, poor survival, metastasis, and resistance to treatment. We have hypo...
Conference Paper
Medullary thyroid cancer (MTC) is a type of neuroendocrine cancer (NE) with increasing incidence worldwide. Compared with well-differentiated thyroid cancers, distant metastases are more commonly observed in MTC patients, ranging from 7-23%. The inability to treat metastatic MTC contributes to a decreased patient survival rate. Currently, at least...
Conference Paper
Medullary thyroid cancer (MTC) is a type of neuroendocrine cancer (NE) with increasing incidence worldwide. Compared with well-differentiated thyroid cancers, distant metastases are more commonly observed in MTC patients, ranging from 7-23%. The inability to treat metastatic MTC contributes to a decreased patient survival rate. Currently, at least...
Conference Paper
p>Hepatocellular carcinoma (HCC) poses a major public health problem worldwide and novel, effective therapeutic approaches for this devastating disease are urgently needed. The overexpression or activation of the MDM2 oncogene frequently occurs in HCC and is linked to cancer growth, poor survival, metastasis, and resistance to treatment. We have hy...
Article
Overexpression and activation of the murine double minute 2 (MDM2) or nuclear factor of activated T cells 1 (NFAT1) oncoproteins frequently occur in pancreatic cancer. Most MDM2 inhibitors under development target MDM2-p53 binding and have little or no effect on cancers without functional p53, including pancreatic cancer. Some available compounds i...
Article
Full-text available
Purpose: Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC) is due in part to reduced expression of L-2-HG dehydrogenase (L2HGDH). However, the contribution of L-2-HG to renal carcinogenesis and insight into the biochemistry and targets of this small molecule remains to be elucidated. Experimental design: Genetic and pharma...
Article
Full-text available
Removal of oral biofilms involves the use of broad-spectrum antimicrobials, which eradicate both pathogenic and protective oral commensal species. Ideal therapeutics for dental caries should be able to selectively inhibit pathogenic biofilms caused by Streptococcus mutans. S. mutans extracellular glucosyltransferases (Gtfs), particularly GtfB and G...
Article
Background: The D-enantiomer of 2-hydroxygultarate (D-2HG), along with fumarate and succinate, are considered oncometabolites that promote tumorigenesis. Our lab has reported elevated levels of the L-enantiomer of 2-hydroxyglutare (L-2HG) in clear cell renal cell carcinoma (ccRCC), in part due to reduced expression of the enzyme L-2HG dehydrogenase...
Article
Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and the important roles that they play in excitable cells. Recently, their presence has been recognized in non-excitable cells such as cancer cells and their overexpression has been shown to be assoc...
Article
Murrayaquinones A–D is a group of four bioactive carbazole-1,4-dione natural products isolated from the root bark of the plant Murraya eucrestifolia hayata. Murrayaquinone is synthesized in five steps starting from the commercially available 2,4,5-trimethoxybenzaldehyde with an overall yield of 45%. The novelty of this murrayaquinone synthesis is i...
Article
Full-text available
Streptococcus mutans employs a key virulence factor, three glucosyltransferase (GtfBCD) enzymes to establish cariogenic biofilms. Therefore, the inhibition of GtfBCD would provide anti-virulence therapeutics. Here a small molecule library of 500,000 small molecule compounds was screened in silico against the available crystal structure of the GtfC...
Article
Statement of significance: Many potent anticancer drugs are hydrophobic and lack tumor selectivity, which limits their application in cancer therapy. Although cubical hydrogels of poly(methacrylic acid) exhibit excellent biocompatibility and versatility, they have not been investigated for hydrophobic drug delivery due to poor mechanical stability...
Article
Full-text available
Bisphosphonates are standard treatments for bone metastases. When given in the adjuvant setting, they reduce breast cancer mortality and recurrence in bone but only among post-menopausal patients. Optimal drug use would require biomarker-based patient selection. Such biomarkers are not yet in clinical use. Based on the similarities in inflammatory...
Article
_Streptococcus mutans_ has been implicated as the major etiological agent in the initiation and the development of dental caries due to its robust capacity to form tenacious biofilms. Ideal therapeutics for this disease will aim to selectively inhibit the biofilm formation process while preserving the natural bacterial flora of the mouth. Several s...
Article
Natural products and their derivatives represent a rich source for the discovery and development of new cancer therapeutic drugs. Bioactive components derived from natural sources including marine compounds have been shown to be effective agents in the clinic or in preclinical settings. In the present review, we present a story of discovery, synthe...
Article
Full-text available
The marine environment is host to unparalleled biological and chemical diversity, making it an attractive resource for the discovery of new therapeutics for a plethora of diseases. Compounds that are extracted from cyanobacteria are of special interest due to their unique structural scaffolds and capacity to produce potent pharmaceutical and biotec...
Article
Full-text available
Many cancer cells follow an aberrant metabolic program to maintain energy for rapid cell proliferation. Metabolic reprogramming often involves the upregulation of glutaminolysis to generate reducing equivalents for the electron transport chain and amino acids for protein synthesis. Critical enzymes involved in metabolism possess a reactive thiolate...
Data
Supplementary material Figure S1: Basal ECAR of MB231 and MCF10A cells in response to BTPP or IBTP. MB231 cells were treated with vehicle (EtOH), IBTP (0.01-10 µM), or BTPP (0.01-10 µM) for 24 h and basal ECAR was measured in parallel with the mitochondrial stress tests described in Fig. 1, Fig. 2. Panel A: Dose response of IBTP or BTPP on basal EC...
Data
Supplementary material Figure S2: Adenine nucleotide levels replotted as % of control. Adenine nucleotide levels measured by HPLC analysis from Fig. 5 are replotted, and values are expressed as % of vehicle control at each time point ±SEM obtained from 3 separate experiments. *P<0.05 compared to vehicle and #P<0.05 IBTP compared to BTPP.
Data
Supplementary material Figure S3: Validation of IBTP effects on GAC protein levels. MB231 cells were treated with IBTP (10 µM) or BTPP (10 µM) for the indicated times (4-24h), or were treated for 24 h followed by removal of the treatment and recovery for 24 or 48 h. Panel A: Image from Western blot analysis using a monoclonal anti-GAC/KGA/GAM antib...
Data
Supplementary material Figure S4: Time course of TPP adduct formation. MB231 cells were treated with either IBTP (10 µM) or BTPP (10 µM) for the indicated times. Cell lysates were prepared and protein adducts were visualized by Western blot analysis using an antibody directed against the TPP moiety (1:3000). Open arrows indicated by the ˃ symbol sh...
Article
Full-text available
In this study, we present data indicating a robust and specific domain interaction between the CFTR first cytosolic loop (CL1) and nucleotide binding domain 1 (NBD1) that allows ion transport to proceed in a regulated fashion. We used co-precipitation and ELISA to establish the molecular contact and showed binding kinetics were not altered by the c...
Article
Mitochondrial metabolism is an essential biological process that generates both energy and signaling mediators, and perturbations by increased oxidative stress can cause metabolic dysfunction which has been shown to play an important role in pathologies such as cardiovascular disease, neurodegenerative disorders, and cancer. Our recent work demonst...
Article
The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine, have been isolated from various marine organisms. A class of pyrroloiminoquinone-related alkaloids, known as bi...
Article
Traditionally, natural products have played a major role in drug discovery by serving as the source of earliest medicine. In spite of the scientific advancements and the promise of alternative drug discovery strategies in the recent decades, there is still a shortage of drugs leading to clinical trials for various diseases. Calothrixin B and its N-...
Article
We have recently designed and synthesized several novel iminoquinone anticancer agents that have entered preclinical development for the treatment of human cancers. Herein we developed and validated a quantitative HPLC-MS/MS analytical method for one of the lead novel anticancer makaluvamine analog, TCBA-TPQ, and conducted a pharmacokinetic study i...
Article
Full-text available
Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC- 5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with...
Article
Full-text available
Despite advances in screening and treatment over the past several years, breast cancer remains a leading cause of cancer-related death among women in the United States. A major goal in breast cancer treatment is to develop safe and clinically useful therapeutic agents that will prevent the recurrence of breast cancers after front-line therapeutics...
Article
Full-text available
Through unbiased metabolomics, we identifi ed elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglu-taratre (2-OG)–dependent dioxygenases that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifi cally the d enantiomer, can result from gain-of-function...
Article
Full-text available
Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their ant...
Article
Full-text available
Unlabelled: Through unbiased metabolomics, we identified elevations of the metabolite 2-hydroxyglutarate (2HG) in renal cell carcinoma (RCC). 2HG can inhibit 2-oxoglutaratre (2-OG)-dependent dioxygenases that mediate epigenetic events, including DNA and histone demethylation. 2HG accumulation, specifically the d enantiomer, can result from gain-of...
Article
Bioactive indolo[3,2-j]phenanthridine alkaloids, calothrixin B and its N-oxide derivative calothrixin A have been synthesized via an oxidative free radical reaction. calothrixin B is generated from the commercially available 2,4,5-trimethoxybenzaldehyde in only 7 steps. The key step in this synthesis is the Mn(OAc)3 mediated oxidative free radical...
Article
Zyzzyanones A-D is a group of biologically active marine alkaloids isolated from Australian marine sponge Zyzzya fuliginosa. They contain a unique bispyrroloquinone ring system as the core structure. The first total synthesis of all four zyzzyanones is described here. The synthesis of these alkaloids started from a previously known 6-benzylamino in...
Article
Identification and validation of molecular targets are considered as a key element in new drug discovery and development. We have recently demonstrated that a novel synthetic iminoquinone analog, termed [7-(benzylamino)-1,3,4,8-tetrahydropyrrolo [4,3, 2-de]quinolin-8(1H)-one] (BA-TPQ), has significant anti-breast cancer activity both in vitro and i...
Article
Full-text available
Nonsense suppression therapy is an approach to treat genetic diseases caused by nonsense mutations. This therapeutic strategy pharmacologically suppresses translation termination at Premature Termination Codons (PTCs) in order to restore expression of functional protein. However, the process of Nonsense-Mediated mRNA Decay (NMD), which reduces the...
Data
Action of UPF1 phosphorylation cycle inhibitors. A) A schematic depicting the UPF1 phosphorylation cycle. The mode of action for caffeine and NMDI-1 on this pathway is shown. B) The structure of NMDI-1. The differences between the NMDI-1 and ellipticine structures are indicated. (PDF)
Data
Full-text available
NMDI-1 increases NMD substrate abundance in mouse tissues. IduaW392X mice were administered 5 mg/kg NMDI-1 for 3 days via once daily subcutaneous injections. After treatment, RNA was isolated from the A) brain, B) heart, and C) spleen and analyzed by RT-qPCR to determine the abundance of Idua, Gas5, and Atf4 NMD substrates (normalized to 18S rRNA o...
Data
Scheme for NMDI-1 synthesis. (PDF)
Data
Full-text available
NMDI-1 co-administration with NB84 for 6 days did not further enhance GAG reduction. IduaW392X mice were treated with NB84 for 14 days alone, or supplemented with NMDI-1 during the final 3 days or the final 6 days of NB84 administration. The GAG levels were quantitated in A) brain, B) heart, and C) spleen. The data shown for each column is the aver...
Data
Full-text available
NMDI-1 does not inhibit protein synthesis or suppress PTCs. A) The effect of various NMD inhibitors on total protein synthesis was determined in HeLa cells. 35S-methionine incorporation per microgram of total protein was monitored in untreated cells (−) or cells treated with NMDI-1 (NI1), caffeine (CAF), ellipticine (ELP), or cycloheximide (CHX) as...
Data
NMD attenuators increase the abundance of endogenous NMD substrates in MEFs. RT-qPCR was used to quantify the steady state abundance of endogenous NMD substrates in A) WT and B) IduaW392X MEFs. The data shown are the mean +/− SD (n = 12) of mRNA abundance in treated MEFs relative to untreated MEFs. mRNA abundance was normalized to either 18S rRNA o...
Data
NMDI-1 alone does not reduce GAG accumulation in IduaW392X mice. The micrograms of GAGs per miiligram of defatted, dried tissue were quantitated in A) brain, B) heart, and C) spleen from WT and MPS I-H mice without (−) and with (+) NMDI-1) treatment. The data shown are the mean +/− sd of 6 replicates derived from 3 mice per group (n = 3). p values...
Conference Paper
Streptococcus mutans is a major aetiological agent of dental caries. Formation of biofilms is a key virulence factor of S. mutans. Drugs that inhibit S. mutans biofilms may have therapeutic potential. Dihydrofolate reductase (DHFR) plays a critical role in regulating the metabolism of folate. DHFR inhibitors are thus potent drugs and have been expl...
Article
Full-text available
Pyrroloquinone ring systems are important structural units present in many biologically active molecules including a number of marine alkaloids. For example, they are found in a series of marine metabolites, such as tsitsikammamines, zyzzyanones, wakayin, and terreusinone. Several of these alkaloids have exhibited antimicrobial, antimalarial, antif...
Article
The marine ecosystem presents an immensely rich chemical and biological resource for the discovery of new anticancer drugs. Recently, marine alkaloids, isolated from various aquatic flora and fauna, have been found to exhibit potent anticancer activities. These compounds range structurally from simple linear peptides to complex macrocyclic polyethe...
Article
Full-text available
Kinase inhibitors are among the fastest growing class of anti-cancer therapies. One family of kinases that has recently gained attention as a target for treating malignant disorders is the Tec kinase family. Evidence has been published that one member of this family; the Bmx kinase, may play a role in the pathogenesis of glioblastoma, prostate, bre...
Article
Full-text available
We have recently designed and synthesized a novel iminoquinone anticancer agent, 7-(4-fluorobenzylamino)-1,3,4,8-tetrahydropyrrolo[4,3,2-de]quinolin-8(1H)-one (FBA-TPQ) and initiated its preclinical development. Herein we investigated its efficacy, safety, and pharmacokinetics in in vitro and in vivo models of human pancreatic cancer. Our results d...
Data
Significant pathways up-regulated by FBA-TPQ. (DOC)
Data
Significant GOs up-regulated by FBA-TPQ. (DOC)
Data
The interaction net of significant pathways. (DOC)
Data
Microarray data support the possible molecular mode of action of FBA-TPQ. A, GO category of the up-regulated genes based on biological processes for differentially expressed genes (p-value<0.05 and FDR<0.05 were used as a threshold to select significant GO categories; LgP is the logarithm of the p-value); B, KEGG pathway analysis of significant pat...